Advertisement

Caveolins and Lung Function

  • Nikolaos A. Maniatis
  • Olga Chernaya
  • Vasily Shinin
  • Richard D. Minshall
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 729)

Abstract

The primary function of the mammalian lung is to facilitate diffusion of oxygen to venous blood and to ventilate carbon dioxide produced by catabolic reactions within cells. However, it is also responsible for a variety of other important functions, including host defense and production of vasoactive agents to regulate not only systemic blood pressure, but also water, electrolyte and acid-base balance. Caveolin-1 is highly expressed in the majority of cell types in the lung, including epithelial, endothelial, smooth muscle, connective tissue cells, and alveolar macrophages. Deletion of caveolin-1 in these cells results in major functional aberrations, suggesting that caveolin-1 may be crucial to lung homeostasis and development. Furthermore, generation of mutant mice that under-express caveolin-1 results in severe functional distortion with phenotypes covering practically the entire spectrum of known lung diseases, including pulmonary hypertension, fibrosis, increased endothelial permeability, and immune defects. In this Chapter, we outline the current state of knowledge regarding caveolin-1-dependent regulation of pulmonary cell functions and discuss recent research findings on the role of caveolin-1 in various pulmonary disease states, including obstructive and fibrotic pulmonary vascular and inflammatory diseases.

Keywords

Lung Function Pulmonary Arterial Hypertension Acute Lung Injury Airway Smooth Muscle Cell Pulmonary Artery Hypertension 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    West JB, Watson RR, Fu Z. The human lung: did evolution get it wrong? Eur Respir J 2007; 29(1):11–17.PubMedCrossRefGoogle Scholar
  2. 2.
    West JB. Thoughts on the pulmonary blood-gas barrier. Am J Physiol Lung Cell Mol Physiol 2003; 285(3):L501–L513.PubMedGoogle Scholar
  3. 3.
    Gehr P, Bachofen M, Weibel ER. The normal human lung: ultrastructure and morphometric estimation of diffusion capacity. Respir Physiol 1978; 32(2):121–140.PubMedCrossRefGoogle Scholar
  4. 4.
    Phillips CG, Kaye SR. On the asymmetry of bifurcations in the bronchial tree. Respir Physiol 1997; 107(1):85–98.PubMedCrossRefGoogle Scholar
  5. 5.
    Stevens T, Phan S, Frid MG et al. Lung vascular cell heterogeneity: endothelium, smooth muscle, and fibroblasts. Proc Am Thorac Soc 2008; 5(7):783–791.PubMedCrossRefGoogle Scholar
  6. 6.
    Whitsett JA, Wert SE, Weaver TE. Alveolar surfactant homeostasis and the pathogenesis of pulmonary disease. Annu Rev Med 2010; 61:105–119.PubMedCrossRefGoogle Scholar
  7. 7.
    Gosens R, Mutawe M, Martin S et al. Caveolae and caveolins in the respiratory system. Curr Mol Med 2008; 8(8):741–753.PubMedCrossRefGoogle Scholar
  8. 8.
    Anderson RG. The caveolae membrane system. Annu Rev Biochem 1998; 67:199–225.PubMedCrossRefGoogle Scholar
  9. 9.
    Couet J, Li S, Okamoto T et al. Identification of peptide and protein ligands for the caveolin-scaffolding domain. Implications for the interaction of caveolin with caveolae-associated proteins. J Biol Chem 1997; 272(10):6525–6533.PubMedCrossRefGoogle Scholar
  10. 10.
    Li S, Couet J, Lisanti MP. Srctyrosine kinases, Galpha subunits and H-Ras share a common membrane-anchored scaffolding protein, caveolin. Caveolin binding negatively regulates the auto-activation of Src tyrosine kinases. J Biol Chem 1996; 271(46):29182–29190.PubMedCrossRefGoogle Scholar
  11. 11.
    Razani B, Lisanti MP. Caveolin-deficient mice: insights into caveolar function human disease. J Clin Invest 2001; 108(11):1553–1561.PubMedGoogle Scholar
  12. 12.
    Morrisey EE, Hogan BL. Preparing for the first breath: genetic and cellular mechanisms in lung development. Dev Cell 18(1):8–23.Google Scholar
  13. 13.
    Schwarz MA, Caldwell L, Cafasso D et al. Emerging pulmonary vasculature lacks fate specification. Am J Physiol Lung Cell Mol Physiol 2009; 296(1):L71–L81.PubMedCrossRefGoogle Scholar
  14. 14.
    Ramirez MI, Pollack L, Millien G et al. The alpha-isoform of caveolin-1 is a marker of vasculogenesis in early lung development. J Histochem Cytochem 2002; 50(1):33–42.PubMedCrossRefGoogle Scholar
  15. 15.
    Engelman JA, Zhang X, Galbiati F et al. Molecular genetics of the caveolin gene family: implications for human cancers, diabetes, Alzheimer disease, and muscular dystrophy. Am J Hum Genet 1998; 63(6):1578–1587.PubMedCrossRefGoogle Scholar
  16. 16.
    Razani B, Engelman JA, Wang XB et al. Caveolin-1 null mice are viable but show evidence of hyperproliferative and vascular abnormalities. J Biol Chem 2001; 276(41):38121–38138.PubMedGoogle Scholar
  17. 17.
    Zhao YY, Zhao YD, Mirza MK et al. Persistent eNOS activation secondary to caveolin-1 deficiency induces pulmonary hypertension in mice and humans through PKG nitration. J Clin Invest 2009; 119(7):2009–2018.PubMedCrossRefGoogle Scholar
  18. 18.
    Maniatis NA, Shinin V, Schraufnagel DE et al. Increased pulmonary vascular resistance and defective pulmonary artery filling in caveolin-1-/-mice. Am J Physiol Lung Cell Mol Physiol 2008; 294(5):L865–L873.PubMedCrossRefGoogle Scholar
  19. 19.
    Mikol DD, Scherer SS, Duckett SJ et al. Schwann cell caveolin-1 expression increases during myelination and decreases after axotomy. Glia 2002; 38(3):191–199.PubMedCrossRefGoogle Scholar
  20. 20.
    Yang G, Timme TL, Naruishi K et al. Mice with cav-1 gene disruption have benign stromal lesions and compromised epithelial differentiation. Exp Mol Pathol 2008; 84(2):131–140.PubMedCrossRefGoogle Scholar
  21. 21.
    Williams MC. Alveolar type I cells: molecular phenotype and development. Annu Rev Physiol 2003; 65:669–695.PubMedCrossRefGoogle Scholar
  22. 22.
    Fuchs S, Hollins AJ, Laue M et al. Differentiation of human alveolar epithelial cells in primary culture: morphological characterization and synthesis of caveolin-1 and surfactant protein-C. Cell Tissue Res 2003; 311(1):31–45.PubMedCrossRefGoogle Scholar
  23. 23.
    Wang Y, Maciejewski BS, Drouillard D et al. A role for caveolin-1 in mechanotransduction of fetal type II epithelial cells. Am J Physiol Lung Cell Mol Physiol 2010.Google Scholar
  24. 24.
    Clevers H. Wnt/beta-catenin signaling in development and disease. Cell 2006; 127(3):469–480.PubMedCrossRefGoogle Scholar
  25. 25.
    van Amerongen R, Nusse R. Towards an integrated view of Wnt signaling in development. Development 2009; 136(19):3205–3214.PubMedCrossRefGoogle Scholar
  26. 26.
    Galbiati F, Volonte D, Brown AM et al. Caveolin-1 expression inhibits Wnt/beta-catenin/Lef-1 signaling by recruiting beta-catenin to caveolae membrane domains. J Biol Chem 2000; 275(30):23368–23377.PubMedCrossRefGoogle Scholar
  27. 27.
    Mucenski ML, Nation JM, Thitoff AR et al. Beta-catenin regulates differentiation of respiratory epithelial cells in vivo. Am J Physiol Lung Cell Mol Physiol 2005; 289(6):L971–L979.PubMedCrossRefGoogle Scholar
  28. 28.
    Okamoto T, Schlegel A, Scherer PE et al. Caveolins, a family of scaffolding proteins for organizing “preassembled signaling complexes” at the plasma membrane. J Biol Chem 1998; 273(10):5419–5422.PubMedCrossRefGoogle Scholar
  29. 29.
    Dahlin K, Mager EM, Allen L et al. Identification of genes differentially expressed in rat alveolar type I cells. Am J Respir Cell Mol Biol 2004; 31(3):309–316.PubMedCrossRefGoogle Scholar
  30. 30.
    Maina JN. Fundamental structural aspects and features in the bioengineering of the gas exchangers: comparative perspectives. Adv Anat Embryol Cell Biol 2002; 163:III-XII, 1–108.CrossRefGoogle Scholar
  31. 31.
    Gold WA, Murray JF, Nadel JA, eds. Procedures in Respiratory Medicine. Philadelphia: Saunders, 2002.Google Scholar
  32. 32.
    Weibel ER. Morphological basis of alveolar-capillary gas exchange. Physiol Rev 1973; 53(2):419–495.PubMedGoogle Scholar
  33. 33.
    Gil J. Number and distribution of plasmalemmal vesicles in the lung. Fed Proc 1983; 42(8):2414–2418.PubMedGoogle Scholar
  34. 34.
    Gil J, Silage DA, McNiff JM. Distribution of vesicles in cells of air-blood barrier in the rabbit. J Appl Physiol 1981; 50(2):334–340.PubMedGoogle Scholar
  35. 35.
    Borok Z, Liebler JM, Lubman RL et al. Na transport proteins are expressed by rat alveolar epithelial type I cells. Am J Physiol Lung Cell Mol Physiol 2002; 282(4):L599–L608.PubMedGoogle Scholar
  36. 36.
    Johnson MD, Widdicombe JH, Allen L et al. Alveolar epithelial type I cells contain transport proteins and transport sodium, supporting an active role for type I cells in regulation of lung liquid homeostasis. Proc Natl Acad Sci U S A 2002; 99(4):1966–1971.PubMedCrossRefGoogle Scholar
  37. 37.
    Dobbs LG, Gonzalez R, Matthay MA et al. Highly water-permeable type I alveolar epithelial cells confer high water permeability between the airspace and vasculature in rat lung. Proc Natl Acad Sci U S A 1998; 95(6):2991–2996.PubMedCrossRefGoogle Scholar
  38. 38.
    Newman GR, Campbell L, von Ruhland C et al. Caveolin and its cellular and subcellular immunolocalisation in lung alveolar epithelium: implications for alveolar epithelial type I cell function. Cell Tissue Res 1999; 295(1):111–120.PubMedCrossRefGoogle Scholar
  39. 39.
    Gumbleton M. Caveolae as potential macromolecule trafficking compartments within alveolar epithelium. Adv Drug Deliv Rev 2001; 49(3):281–300.PubMedCrossRefGoogle Scholar
  40. 40.
    Atwal OS, Viel L, Minhas KJ. An uptake of cationized ferritin by alveolar type I cells in airway-instilled goat lung: distribution of anionic sites on the epithelial surface. J Submicrosc Cytol Pathol 1990; 22(3):425–432.PubMedGoogle Scholar
  41. 41.
    Kasper M, Reimann T, Hempel U et al. Loss of caveolin expression in type I pneumocytes as an indicator of subcellular alterations during lung fibrogenesis. Histochem Cell Biol 1998; 109(1):41–48.PubMedCrossRefGoogle Scholar
  42. 42.
    Andreeva AV, Kutuzov MA, Voyno-Yasenetskaya TA. Regulation of surfactant secretion in alveolar type II cells. Am J Physiol Lung Cell Mol Physiol 2007; 293(2):L259–L271.PubMedCrossRefGoogle Scholar
  43. 43.
    Campbell L, Hollins AJ, Al-Eid A et al. Caveolin-1 expression and caveolae biogenesis during cell transdifferentiation in lung alveolar epithelial primary cultures. Biochem Biophys Res Commun 1999; 262(3):744–751.PubMedCrossRefGoogle Scholar
  44. 44.
    Bignon J, Jaurand MC, Pinchon MC et al. Immunoelectron microscopic and immunochemical demonstrations of serum proteins in the alveolar lining material of the rat lung. Am Rev Respir Dis 1976; 113(2):109–120.PubMedGoogle Scholar
  45. 45.
    Kogo H, Aiba T, Fujimoto T. Cell type-specific occurrence of caveolin-1alpha and-1beta in the lung caused by expression of distinct mRNAs. J Biol Chem 2004; 279(24):25574–25581.PubMedCrossRefGoogle Scholar
  46. 46.
    Peterson BT, Idell S, MacArthur C et al. A modified bronchoalveolar lavage procedure that allows measurement of lung epithelial lining fluid volume. Am Rev Respir Dis 1990; 141(2):314–320.PubMedGoogle Scholar
  47. 47.
    Peterson BT, Griffith DE, Tate RW et al. Single-cycle bronchoalveolar lavage to determine solute concentrations in epithelial lining fluid. Am Rev Respir Dis 1993; 147(5):1216–1222.PubMedGoogle Scholar
  48. 48.
    Pusch R, Kleen M, Habler O et al. Biochemical and cellular composition of alveolar epithelial lining fluid in anesthetized healthy lambs. Eur J Med Res 1997; 2(12):499–505.PubMedGoogle Scholar
  49. 49.
    Hastings RH, Wright JR, Albertine KH et al. Effect of endocytosis inhibitors on alveolar clearance of albumin, immunoglobulin G, and SP-A in rabbits. Am J Physiol 1994; 266(5 Pt 1):L544–L552.PubMedGoogle Scholar
  50. 50.
    Hastings RH, Folkesson HG, Petersen V et al. Cellular uptake of albumin from lungs of anesthetized rabbits. Am J Physiol 1995; 269(4 Pt 1):L453–L462.PubMedGoogle Scholar
  51. 51.
    Hastings RH, Folkesson HG, Matthay MA. Mechanisms of alveolar protein clearance in the intact lung. Am J Physiol Lung Cell Mol Physiol 2004; 286(4):L679–L689.PubMedCrossRefGoogle Scholar
  52. 52.
    John TA, Vogel SM, Minshall RD et al. Evidence for the role of alveolar epithelial gp60 in active transalveolar albumin transport in the rat lung. J Physiol 2001; 533(Pt 2):547–559.PubMedCrossRefGoogle Scholar
  53. 53.
    Ware LB, Matthay MA. Clinical practice. Acute pulmonary edema. N Engl J Med 2005; 353(26):2788–2796.PubMedCrossRefGoogle Scholar
  54. 54.
    Orfanos SE, Mavrommati I, Korovesi I et al. Pulmonary endothelium in acute lung injury: from basic science to the critically ill. Intensive Care Med 2004; 30(9):1702–1714.PubMedCrossRefGoogle Scholar
  55. 55.
    Maniatis NA, Orfanos SE. The endothelium in acute lung injury/acute respiratory distress syndrome. Curr Opin Crit Care 2008; 14(1):22–30.PubMedCrossRefGoogle Scholar
  56. 56.
    Maniatis NA, Kotanidou A, Catravas JD et al. Endothelial pathomechanisms in acute lung injury. Vascul Pharmacol 2008; 49(4–6):119–133.PubMedCrossRefGoogle Scholar
  57. 57.
    Predescu SA, Predescu DN, Malik AB. Molecular determinants of endothelial transcytosis and their role in endothelial permeability. Am J Physiol Lung Cell Mol Physiol 2007; 293(4):L823–L842.PubMedCrossRefGoogle Scholar
  58. 58.
    Mehta D, Malik AB. Signaling mechanisms regulating endothelial permeability. Physiol Rev 2006; 86(1):279–367.PubMedCrossRefGoogle Scholar
  59. 59.
    Minshall RD, Malik AB. Transport across the endothelium: regulation of endothelial permeability. Handb Exp Pharmacol 2006; (176 Pt 1):107–144.Google Scholar
  60. 60.
    Schnitzer JE, Allard J, Oh P. NEM inhibits transcytosis, endocytosis, and capillary permeability: implication of caveolae fusion in endothelia. Am J Physiol 1995; 268(1 Pt 2):H48–H55.PubMedGoogle Scholar
  61. 61.
    Tiruppathi C, Song W, Bergenfeldt M et al. Gp60 activation mediates albumin transcytosis in endothelial cells by tyrosine kinase-dependent pathway. J Biol Chem 1997; 272(41):25968–25975.PubMedCrossRefGoogle Scholar
  62. 62.
    Minshall RD, Tiruppathi C, Vogel SM et al. Endothelial cell-surface gp60 activates vesicle formation and trafficking via G(i)-coupled Src kinase signaling pathway. J Cell Biol 2000; 150(5):1057–1070.PubMedCrossRefGoogle Scholar
  63. 63.
    John TA, Vogel SM, Tiruppathi C et al. Quantitative analysis of albumin uptake and transport in the rat microvessel endothelial monolayer. Am J Physiol Lung Cell Mol Physiol 2003; 284(1):L187–L196.PubMedGoogle Scholar
  64. 64.
    Shajahan AN, Timblin BK, Sandoval R et al. Role of Src-induced dynamin-2 phosphorylation in caveolae-mediated endocytosis in endothelial cells. J Biol Chem 2004; 279(19):20392–20400.PubMedCrossRefGoogle Scholar
  65. 65.
    Shajahan AN, Tiruppathi C, Smrcka AV et al. Gbetagamma activation of Src induces caveolae-mediated endocytosis in endothelial cells. J Biol Chem 2004; 279(46):48055–48062.PubMedCrossRefGoogle Scholar
  66. 66.
    Minshall RD, Tiruppathi C, Vogel SM et al. Vesicle formation and trafficking in endothelial cells and regulation of endothelial barrier function. Histochem Cell Biol 2002; 117(2):105–112.PubMedCrossRefGoogle Scholar
  67. 67.
    Parkar NS, Akpa BS, Nitsche LC et al. Vesicle formation and endocytosis: function, machinery, mechanisms, and modeling. Antioxid Redox Signal 2009; 11(6):1301–1312.PubMedCrossRefGoogle Scholar
  68. 68.
    Maniatis NA, Brovkovych V, Allen SE et al. Novel mechanism of endothelial nitric oxide synthase activation mediated by caveolae internalization in endothelial cells. Circ Res 2006; 99(8):870–877.PubMedCrossRefGoogle Scholar
  69. 69.
    Schnitzer JE, Oh P. Aquaporin-1 in plasma membrane and caveolae provides mercury-sensitive water channels across lung endothelium. Am J Physiol 1996; 270(1 Pt 2):H416–H422.PubMedGoogle Scholar
  70. 70.
    Zhang XL, Topley N, Ito T et al. Interleukin-6 regulation of transforming growth factor (TGF)-beta receptor compartmentalization and turnover enhances TGF-beta1 signaling. J Biol Chem 2005; 280(13):12239–12245.PubMedCrossRefGoogle Scholar
  71. 71.
    Schubert W, Frank PG, Woodman SE et al. Microvascular hyperpermeability in caveolin-1 (−/−) knock-out mice. Treatment with a specific nitric-oxide synthase inhibitor, L-NAME, restores normal microvascular permeability in Cav-1 null mice. J Biol Chem 2002; 277(42):40091–40098.PubMedCrossRefGoogle Scholar
  72. 72.
    Miyawaki-Shimizu K, Predescu D, Shimizu J et al. siRNA-induced caveolin-1 knockdown in mice increases lung vascular permeability via the junctional pathway. Am J Physiol Lung Cell Mol Physiol 2006; 290(2):L405–L413.PubMedCrossRefGoogle Scholar
  73. 73.
    Sun Y, Hu G, Zhang X et al. Phosphorylation of caveolin-1 regulates oxidant-induced pulmonary vascular permeability via paracellular and transcellular pathways. Circ Res 2009; 105(7):676–685, 615 p following 685.PubMedCrossRefGoogle Scholar
  74. 74.
    Hu G, Vogel SM, Schwartz DE et al. Intercellular adhesion molecule-1-dependent neutrophil adhesion to endothelial cells induces caveolae-mediated pulmonary vascular hyperpermeability. Circ Res 2008; 102(12):e120–e131.PubMedCrossRefGoogle Scholar
  75. 75.
    Smith P, Heath D, Yacoub M et al. The ultrastructure of plexogenic pulmonary arteriopathy. J Pathol 1990; 160(2):111–121.PubMedCrossRefGoogle Scholar
  76. 76.
    Dorfmuller P, Humbert M, Capron F et al. Pathology and aspects of pathogenesis in pulmonary arterial hypertension. Sarcoidosis Vasc Diffuse Lung Dis 2003; 20(1):9–19.PubMedGoogle Scholar
  77. 77.
    Sakao S, Tatsumi K, Voelkel NF. Endothelial cells and pulmonary arterial hypertension: apoptosis, proliferation, interaction and transdifferentiation. Respir Res 2009; 10:95.PubMedCrossRefGoogle Scholar
  78. 78.
    Simonneau G, Robbins IM, Beghetti M et al. Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol 2009; 54(1 Suppl):S43–S54.PubMedCrossRefGoogle Scholar
  79. 79.
    Tuder RM, Groves B, Badesch DB et al. Exuberant endothelial cell growth and elements of inflammation are present in plexiform lesions of pulmonary hypertension. Am J Pathol 1994; 144(2):275–285.PubMedGoogle Scholar
  80. 80.
    Cool CD, Groshong SD, Oakey J et al. Pulmonary hypertension: cellular and molecular mechanisms. Chest 2005; 128(6 Suppl):565S–571S.PubMedCrossRefGoogle Scholar
  81. 81.
    Sakao S, Taraseviciene-Stewart L, Lee JD et al. Initial apoptosis is followed by increased proliferation of apoptosis-resistant endothelial cells. FASEB J 2005; 19(9):1178–1180.PubMedGoogle Scholar
  82. 82.
    Sehgal PB, Mukhopadhyay S. Dysfunctional intracellular trafficking in the pathobiology of pulmonary arterial hypertension. Am J Respir Cell Mol Biol 2007; 37(1):31–37.PubMedCrossRefGoogle Scholar
  83. 83.
    Smith P, Heath D. Electron microscopy of the plexiform lesion. Thorax 1979; 34(2):177–186.PubMedCrossRefGoogle Scholar
  84. 84.
    Heath D, Smith P, Gosney J et al. The pathology of the early and late stages of primary pulmonary hypertension. Br Heart J 1987; 58(3):204–213.PubMedCrossRefGoogle Scholar
  85. 85.
    Geraci MW, Moore M, Gesell T et al. Gene expression patterns in the lungs of patients with primary pulmonary hypertension: a gene microarray analysis. Circ Res 2001; 88(6):555–562.PubMedGoogle Scholar
  86. 86.
    Achcar RO, Demura Y, Rai PR et al. Loss of caveolin and heme oxygenase expression in severe pulmonary hypertension. Chest 2006; 129(3):696–705.PubMedCrossRefGoogle Scholar
  87. 87.
    Mathew R, Huang J, Shah M et al. Disruption of endothelial-cell caveolin-1alpha/raft scaffolding during development of monocrotaline-induced pulmonary hypertension. Circulation 2004; 110(11):1499–1506.PubMedCrossRefGoogle Scholar
  88. 88.
    Mukhopadhyay S, Xu F, Sehgal PB. Aberrant cytoplasmic sequestration of eNOS in endothelial cells after monocrotaline, hypoxia, and senescence: live-cell caveolar and cytoplasmic NO imaging. Am J Physiol Heart Circ Physiol 2007; 292(3):H1373–H1389.PubMedCrossRefGoogle Scholar
  89. 89.
    Jasmin JF, Mercier I, Dupuis J et al. Short-term administration of a cell-permeable caveolin-1 peptide prevents the development of monocrotaline-induced pulmonary hypertension and right ventricular hypertrophy. Circulation 2006; 114(9):912–920.PubMedCrossRefGoogle Scholar
  90. 90.
    Zhao YY, Liu Y, Stan RV et al. Defects in caveolin-1 cause dilated cardiomyopathy and pulmonary hypertension in knockout mice. Proc Natl Acad Sci U S A 2002; 99(17):11375–11380.PubMedCrossRefGoogle Scholar
  91. 91.
    Wunderlich C, Schober K, Lange SA et al. Disruption of caveolin-1 leads to enhanced nitrosative stress and severe systolic and diastolic heart failure. Biochem Biophys Res Commun 2006; 340(2):702–708.PubMedCrossRefGoogle Scholar
  92. 92.
    Wunderlich C, Schober K, Schmeisser A et al. The adverse cardiopulmonary phenotype of caveolin-1 deficient mice is mediated by a dysfunctional endothelium. J Mol Cell Cardiol 2008; 44(5):938–947.PubMedCrossRefGoogle Scholar
  93. 93.
    Wunderlich C, Schmeisser A, Heerwagen C et al. Chronic NOS inhibition prevents adverse lung remodeling and pulmonary arterial hypertension in caveolin-1 knockout mice. Pulm Pharmacol Ther 2008; 21(3):507–515.PubMedCrossRefGoogle Scholar
  94. 94.
    Zhao YY, Malik AB. A novel insight into the mechanism of pulmonary hypertension involving caveolin-1 deficiency and endothelial nitric oxide synthase activation. Trends Cardiovasc Med 2009; 19(7):238–242.PubMedCrossRefGoogle Scholar
  95. 95.
    Khalil N, O’Connor RN, Flanders KC et al. TGF-beta 1, but not TGF-beta 2 or TGF-beta 3, is differentially present in epithelial cells of advanced pulmonary fibrosis: an immunohistochemical study. Am J Respir Cell Mol Biol 1996; 14(2):131–138.PubMedGoogle Scholar
  96. 96.
    Khalil N, O’Connor RN, Unruh HW et al. Increased production and immunohistochemical localization of transforming growth factor-beta in idiopathic pulmonary fibrosis. Am J Respir Cell Mol Biol 1991; 5(2):155–162.PubMedGoogle Scholar
  97. 97.
    Khalil N, O’Connor RN, Flanders KC et al. Regulation of type II alveolar epithelial cell proliferation by TGF-beta during bleomycin-induced lung injury in rats. Am J Physiol 1994; 267(5 Pt 1):L498–L507.PubMedGoogle Scholar
  98. 98.
    Verma S, Slutsky AS. Idiopathic pulmonary fibrosis-new insights. N Engl J Med 2007; 356(13):1370–1372.PubMedCrossRefGoogle Scholar
  99. 99.
    Varga J, Abraham D. Systemic sclerosis: a prototypic multisystem fibrotic disorder. J Clin Invest 2007; 117(3):557–567.PubMedCrossRefGoogle Scholar
  100. 100.
    Del Galdo F, Lisanti MP, Jimenez SA. Caveolin-1, transforming growth factor-beta receptor internalization and the pathogenesis of systemic sclerosis. Curr Opin Rheumatol 2008; 20(6):713–719.PubMedCrossRefGoogle Scholar
  101. 101.
    Drab M, Verkade P, Elger M et al. Loss of caveolae, vascular dysfunction, and pulmonary defects in caveolin-1 gene-disrupted mice. Science 2001; 293(5539):2449–2452.PubMedCrossRefGoogle Scholar
  102. 102.
    Le Saux O, Teeters K, Miyasato S et al. The role of caveolin-1 in pulmonary matrix remodeling and mechanical properties. Am J Physiol Lung Cell Mol Physiol 2008; 295(6):L1007–L1017.PubMedCrossRefGoogle Scholar
  103. 103.
    Murata T, Lin MI, Huang Y et al. Reexpression of caveolin-1 in endothelium rescues the vascular, cardiac, and pulmonary defects in global caveolin-1 knockout mice. J Exp Med 2007; 204(10):2373–2382.PubMedCrossRefGoogle Scholar
  104. 104.
    Odajima N, Betsuyaku T, Nasuhara Y et al. Loss of caveolin-1 in bronchiolization in lung fibrosis. J Histochem Cytochem 2007; 55(9):899–909.PubMedCrossRefGoogle Scholar
  105. 105.
    Tourkina E, Gooz P, Pannu J et al. Opposing effects of protein kinase Calpha and protein kinase Cepsilon on collagen expression by human lung fibroblasts are mediated via MEK/ERK and caveolin-1 signaling. J Biol Chem 2005; 280(14):13879–13887.PubMedCrossRefGoogle Scholar
  106. 106.
    Wang XM, Zhang Y, Kim HP et al. Caveolin-1: a critical regulator of lung fibrosis in idiopathic pulmonary fibrosis. J Exp Med 2006; 203(13):2895–2906.PubMedCrossRefGoogle Scholar
  107. 107.
    Del Galdo F, Sotgia F, de Almeida CJ et al. Decreased expression of caveolin 1 in patients with systemic sclerosis: crucial role in the pathogenesis of tissue fibrosis. Arthritis Rheum 2008; 58(9):2854–2865.PubMedCrossRefGoogle Scholar
  108. 108.
    Tourkina E, Richard M, Gooz P et al. Antifibrotic properties of caveolin-1 scaffolding domain in vitro and in vivo. Am J Physiol Lung Cell Mol Physiol 2008; 294(5):L843–L861.PubMedCrossRefGoogle Scholar
  109. 109.
    Chen YG. Endocytic regulation of TGF-beta signaling. Cell Res 2009; 19(1):58–70.PubMedCrossRefGoogle Scholar
  110. 110.
    Hayes S, Chawla A, Corvera S. TGF beta receptor internalization into EEA1-enriched early endosomes: role in signaling to Smad2. J Cell Biol 2002; 158(7):1239–1249.PubMedCrossRefGoogle Scholar
  111. 111.
    Di Guglielmo GM, Le Roy C, Goodfellow AF et al. Distinct endocytic pathways regulate TGF-beta receptor signalling and turnover. Nat Cell Biol 2003; 5(5):410–421.PubMedCrossRefGoogle Scholar
  112. 112.
    Runyan CE, Schnaper HW, Poncelet AC. The role of internalization in transforming growth factor beta1-induced Smad2 association with Smad anchor for receptor activation (SARA) and Smad2-dependent signaling in human mesangial cells. J Biol Chem 2005; 280(9):8300–8308.PubMedCrossRefGoogle Scholar
  113. 113.
    Bousquet J, Jeffery PK, Busse WW et al. Asthma. From bronchoconstriction to airways inflammation and remodeling. Am J Respir Crit Care Med 2000; 161(5):1720–1745.PubMedGoogle Scholar
  114. 114.
    Camoretti-Mercado B. Targeting the airway smooth muscle for asthma treatment. Transl Res 2009; 154(4):165–174.PubMedCrossRefGoogle Scholar
  115. 115.
    Murphy DM, O’Byrne PM. Recent advances in the pathophysiology of asthma. Chest 2010; 137(6): 1417–1426.PubMedCrossRefGoogle Scholar
  116. 116.
    Halayko AJ, Tran T, Gosens R. Phenotype and functional plasticity of airway smooth muscle: role of caveolae and caveolins. Proc Am Thorac Soc 2008; 5(1):80–88.PubMedCrossRefGoogle Scholar
  117. 117.
    Owens GK. Regulation of differentiation of vascular smooth muscle cells. Physiol Rev 1995; 75(3):487–517.PubMedGoogle Scholar
  118. 118.
    Owens GK, Kumar MS, Wamhoff BR. Molecular regulation of vascular smooth muscle cell differentiation in development and disease. Physiol Rev 2004; 84(3):767–801.PubMedCrossRefGoogle Scholar
  119. 119.
    Hirst SJ, Twort CH, Lee TH. Differential effects of extracellular matrix proteins on human airway smooth muscle cell proliferation and phenotype. Am J Respir Cell Mol Biol 2000; 23(3):335–344.PubMedGoogle Scholar
  120. 120.
    Dekkers BG, Schaafsma D, Tran T et al. Insulin-induced laminin expression promotes a hypercontractile airway smooth muscle phenotype. Am J Respir Cell Mol Biol 2009; 41(4):494–504.PubMedCrossRefGoogle Scholar
  121. 121.
    Dekkers BG, Schaafsma D, Nelemans SA et al. Extracellular matrix proteins differentially regulate airway smooth muscle phenotype and function. Am J Physiol Lung Cell Mol Physiol 2007; 292(6):L1405–L1413.PubMedCrossRefGoogle Scholar
  122. 122.
    Schaafsma D, McNeill KD, Stelmack GL et al. Insulin increases the expression of contractile phenotypic markers in airway smooth muscle. Am J Physiol Cell Physiol 2007; 293(1):C429–C439.PubMedCrossRefGoogle Scholar
  123. 123.
    Peterson TE, Guicciardi ME, Gulati R et al. Caveolin-1 can regulate vascular smooth muscle cell fate by switching platelet-derived growth factor signaling from a proliferative to an apoptotic pathway. Arterioscler Thromb Vasc Biol 2003; 23(9):1521–1527.PubMedCrossRefGoogle Scholar
  124. 124.
    Thyberg J, Roy J, Tran PK et al. Expression of caveolae on the surface of rat arterial smooth muscle cells is dependent on the phenotypic state of the cells. Lab Invest 1997; 77(1):93–101.PubMedGoogle Scholar
  125. 125.
    Zhang Y, Peng F, Gao B et al. Mechanical Strain-Induced RhoA Activation Requires NADPH Oxidase-Mediated ROS Generation in Caveolae. Antioxid Redox Signal 2010.Google Scholar
  126. 126.
    Peng F, Zhang B, Wu D et al. TGFbeta-induced RhoA activation and fibronectin production in mesangial cells require caveolae. Am J Physiol Renal Physiol 2008; 295(1):F153–F164.PubMedCrossRefGoogle Scholar
  127. 127.
    Somara S, Gilmont RR, Martens JR et al. Ectopic expression of caveolin-1 restores physiological contractile response of aged colonic smooth muscle. Am J Physiol Gastrointest Liver Physiol 2007; 293(1):G240–G249.PubMedCrossRefGoogle Scholar
  128. 128.
    Hunter I, Nixon GF. Spatial compartmentalization of tumor necrosis factor (TNF) receptor 1-dependent signaling pathways in human airway smooth muscle cells. Lipid rafts are essential for TNF-alpha-mediated activation of RhoA but dispensable for the activation of the NF-kappaB and MAPK pathways. J Biol Chem 2006; 281(45):34705–34715.PubMedCrossRefGoogle Scholar
  129. 129.
    Gosens R, Dueck G, Gerthoffer WT et al. p42/p44 MAP kinase activation is localized to caveolae-free membrane domains in airway smooth muscle. Am J Physiol Lung Cell Mol Physiol 2007; 292(5): L1163–L1172.PubMedCrossRefGoogle Scholar
  130. 130.
    Le Saux CJ, Teeters K, Miyasato SK et al. Down-regulation of caveolin-1, an inhibitor of transforming growth factor-beta signaling, in acute allergen-induced airway remodeling. J Biol Chem 2008; 283(9):5760–5768.PubMedCrossRefGoogle Scholar
  131. 131.
    Mercer J, Schelhaas M, Helenius A. Virus entry by endocytosis. Annu Rev Biochem 79:803–833.Google Scholar
  132. 132.
    Zaas DW, Duncan MJ, Li G et al. Pseudomonas invasion of type I pneumocytes is dependent on the expression and phosphorylation of caveolin-2. J Biol Chem 2005; 280(6):4864–4872.PubMedCrossRefGoogle Scholar
  133. 133.
    Millan J, Hewlett L, Glyn M et al. Lymphocyte transcellular migration occurs through recruitment of endothelial ICAM-1 to caveola-and F-actin-rich domains. Nat Cell Biol 2006; 8(2):113–123.PubMedCrossRefGoogle Scholar
  134. 134.
    Tiruppathi C, Shimizu J, Miyawaki-Shimizu K et al. Role of NF-kappaB-dependent caveolin-1 expression in the mechanism of increased endothelial permeability induced by lipopolysaccharide. J Biol Chem 2008; 283(7):4210–4218.PubMedCrossRefGoogle Scholar
  135. 135.
    Hatakeyama T, Pappas PJ, Hobson RW 2nd et al. Endothelial nitric oxide synthase regulates microvascular hyperpermeability in vivo. J Physiol 2006; 574(Pt 1):275–281.PubMedCrossRefGoogle Scholar
  136. 136.
    Sessa WC. eNOS at a glance. J Cell Sci 2004; 117(Pt 12):2427–2429.PubMedCrossRefGoogle Scholar
  137. 137.
    Zhou X, He P. Endothelial [Ca2+]i and caveolin-1 antagonistically regulate eNOS activity and microvessel permeability in rat venules. Cardiovasc Res 87(2):340–347.Google Scholar
  138. 138.
    Bucci M, Gratton JP, Rudic RD et al. In vivo delivery of the caveolin-1 scaffolding domain inhibits nitric oxide synthesis and reduces inflammation. Nat Med 2000; 6(12):1362–1367.PubMedCrossRefGoogle Scholar
  139. 139.
    Garrean S, Gao XP, Brovkovych V et al. Caveolin-1 regulates NF-kappaB activation and lung inflammatory response to sepsis induced by lipopolysaccharide. J Immunol 2006; 177(7):4853–4860.PubMedGoogle Scholar
  140. 140.
    Mirza MK, Yuan J, Gao XP et al. Caveolin-1 deficiency dampens Toll-like receptor 4 signaling through eNOS activation. Am J Pathol 176(5):2344–2351.Google Scholar
  141. 141.
    Medina FA, de Almeida CJ, Dew E et al. Caveolin-1-deficient mice show defects in innate immunity and inflammatory immune response during Salmonella enterica serovar Typhimurium infection. Infect Immun 2006; 74(12):6665–6674.PubMedCrossRefGoogle Scholar
  142. 142.
    Medina FA, Cohen AW, de Almeida CJ et al. Immune dysfunction in caveolin-1 null mice following infection with Trypanosoma cruzi (Tulahuen strain). Microbes Infect 2007; 9(3):325–333.PubMedCrossRefGoogle Scholar
  143. 143.
    Feng H, Guo L, Song Z et al. Caveolin-1 protects against sepsis by modulating inflammatory response, alleviating bacterial burden, and suppressing thymocyte apoptosis. J Biol Chem 285(33):25154–25160.Google Scholar
  144. 144.
    Li J, Scherl A, Medina F et al. Impaired phagocytosis in caveolin-1 deficient macrophages. Cell Cycle 2005; 4(11):1599–1607.PubMedCrossRefGoogle Scholar
  145. 145.
    Hu G, Ye RD, Dinauer MC et al. Neutrophil caveolin-1 expression contributes to mechanism of lung inflammation and injury. Am J Physiol Lung Cell Mol Physiol 2008; 294(2):L178–L186.PubMedCrossRefGoogle Scholar
  146. 146.
    Oakley FD, Smith RL, Engelhardt JF. Lipid rafts and caveolin-1 coordinate interleukin-1beta (IL-1beta)-dependent activation of NFkappaB by controlling endocytosis of Nox2 and IL-1beta receptor 1 from the plasma membrane. J Biol Chem 2009; 284(48):33255–33264.PubMedCrossRefGoogle Scholar
  147. 147.
    Majkova Z, Smart E, Toborek M et al. Up-regulation of endothelial monocyte chemoattractant protein-1 by coplanar PCB77 is caveolin-1-dependent. Toxicol Appl Pharmacol 2009; 237(1):1–7.PubMedCrossRefGoogle Scholar
  148. 148.
    Wang L, Lim EJ, Toborek M et al. The role of fatty acids and caveolin-1 in tumor necrosis factor alpha-induced endothelial cell activation. Metabolism 2008; 57(10):1328–1339.PubMedCrossRefGoogle Scholar
  149. 149.
    Wang XM, Kim HP, Nakahira K et al. The heme oxygenase-1/carbon monoxide pathway suppresses TLR4 signaling by regulating the interaction of TLR4 with caveolin-1. J Immunol 2009; 182(6):3809–3818.PubMedCrossRefGoogle Scholar
  150. 150.
    Schwartz AM, Henson DE. Diagnostic surgical pathology in lung cancer: ACCP evidence-based clinical practice guidelines (2nd edition). Chest 2007; 132(3 Suppl):78S–93S.PubMedCrossRefGoogle Scholar
  151. 151.
    Stinchcombe TE, Socinski MA. Current treatments for advanced stage non-small cell lung cancer. Proc Am Thorac Soc 2009; 6(2):233–241.PubMedCrossRefGoogle Scholar
  152. 152.
    Masson RJ, Broaddus VC, Murray JF et al. Murray and Nadel’s Textbook of Respiratory Medicine, 4th edition. Philadelphia: Saunders, 2005.Google Scholar
  153. 153.
    Jett JR, Schild SE, Keith RL et al. Treatment of non-small cell lung cancer, stage IIIB: ACCP evidence-based clinical practice guidelines (2nd edition). Chest 2007; 132(3 Suppl):266S–276S.PubMedCrossRefGoogle Scholar
  154. 154.
    Glenney JR Jr. Tyrosine phosphorylation of a 22-kDa protein is correlated with transformation by Rous sarcoma virus. J Biol Chem 1989; 264(34):20163–20166.PubMedGoogle Scholar
  155. 155.
    Glenney JR Jr., Soppet D. Sequence and expression of caveolin, a protein component of caveolae plasma membrane domains phosphorylated on tyrosine in Rous sarcoma virus-transformed fibroblasts. Proc Natl Acad Sci U S A 1992; 89(21):10517–10521.PubMedCrossRefGoogle Scholar
  156. 156.
    Glenney JR Jr., Zokas L. Novel tyrosine kinase substrates from Rous sarcoma virus-transformed cells are present in the membrane skeleton. J Cell Biol 1989; 108(6):2401–2408.PubMedCrossRefGoogle Scholar
  157. 157.
    Koleske AJ, Baltimore D, Lisanti MP. Reduction of caveolin and caveolae in oncogenically transformed cells. Proc Natl Acad Sci U S A 1995; 92(5):1381–1385.PubMedCrossRefGoogle Scholar
  158. 158.
    An SS, Bai TR, Bates JH et al. Airway smooth muscle dynamics: a common pathway of airway obstruction in asthma. Eur Respir J 2007; 29(5):834–860.PubMedCrossRefGoogle Scholar
  159. 159.
    Hulit J, Bash T, Fu M et al. The cyclin D1 gene is transcriptionally repressed by caveolin-1. J Biol Chem 2000; 275(28):21203–21209.PubMedCrossRefGoogle Scholar
  160. 160.
    Gratton JP, Lin MI, Yu J et al. Selective inhibition of tumor microvascular permeability by cavtratin blocks tumor progression in mice. Cancer Cell 2003; 4(1):31–39.PubMedCrossRefGoogle Scholar
  161. 161.
    Racine C, Belanger M, Hirabayashi H et al. Reduction of caveolin 1 gene expression in lung carcinoma cell lines. Biochem Biophys Res Commun 1999; 255(3):580–586.PubMedCrossRefGoogle Scholar
  162. 162.
    Wikman H, Kettunen E, Seppanen JK et al. Identification of differentially expressed genes in pulmonary adenocarcinoma by using cDNA array. Oncogene 2002; 21(37):5804–5813.PubMedCrossRefGoogle Scholar
  163. 163.
    Wikman H, Seppanen JK, Sarhadi VK et al. Caveolins as tumour markers in lung cancer detected by combined use of cDNA and tissue microarrays. J Pathol 2004; 203(1):584–593.PubMedCrossRefGoogle Scholar
  164. 164.
    Sunaga N, Miyajima K, Suzuki M et al. Different roles for caveolin-1 in the development of non-small cell lung cancer versus small cell lung cancer. Cancer Res 2004; 64(12):4277–4285.PubMedCrossRefGoogle Scholar
  165. 165.
    Ho CC, Huang PH, Huang HY et al. Up-regulated caveolin-1 accentuates the metastasis capability of lung adenocarcinoma by inducing filopodia formation. Am J Pathol 2002; 161(5):1647–1656.PubMedCrossRefGoogle Scholar
  166. 166.
    Huang J, Kaminski PM, Edwards JG et al. Pyrrolidine dithiocarbamate restores endothelial cell membrane integrity and attenuates monocrotaline-induced pulmonary artery hypertension. Am J Physiol Lung Cell Mol Physiol 2008; 294(6):L1250–L1259.PubMedCrossRefGoogle Scholar
  167. 167.
    Joshi B, Strugnell SS, Goetz JG et al. Phosphorylated caveolin-1 regulates Rho/ROCK-dependent focal adhesion dynamics and tumor cell migration and invasion. Cancer Res 2008; 68(20):8210–8220.PubMedCrossRefGoogle Scholar
  168. 168.
    Bonuccelli G, Casimiro MC, Sotgia F et al. Caveolin-1 (P132L), a common breast cancer mutation, confers mammary cell invasiveness and defines a novel stem cell/metastasis-associated gene signature. Am J Pathol 2009; 174(5):1650–1662.PubMedCrossRefGoogle Scholar
  169. 169.
    Belanger MM, Gaudreau M, Roussel E et al. Role of caveolin-1 in etoposide resistance development in A549 lung cancer cells. Cancer Biol Ther 2004; 3(10):954–959.PubMedCrossRefGoogle Scholar
  170. 170.
    Belanger MM, Roussel E, Couet J. Up-regulation of caveolin expression by cytotoxic agents in drug-sensitive cancer cells. Anticancer Drugs 2003; 14(4):281–287.PubMedCrossRefGoogle Scholar

Copyright information

© Landes Bioscience and Springer Science+Business Media 2012

Authors and Affiliations

  • Nikolaos A. Maniatis
    • 1
  • Olga Chernaya
    • 2
  • Vasily Shinin
    • 2
  • Richard D. Minshall
    • 2
    • 3
    • 4
  1. 1.2nd Department of Critical CareNational and Kapodistrian University of Athens Medical SchoolAthensGreece
  2. 2.Department of PharmacologyUniversity of Illinois at ChicagoChicagoUSA
  3. 3.Department of AnesthesiologyUniversity of Illinois at ChicagoChicagoUSA
  4. 4.Center for Lung and Vascular BiologyUniversity of Illinois at ChicagoChicagoUSA

Personalised recommendations