Molecular and Cellular Biochemistry

, Volume 305, Issue 1–2, pp 163–169 | Cite as

Effect of adenosine in extracellular matrix synthesis in human and rat mesangial cells

  • Carlos Martínez-Salgado
  • Begoña García-Cenador
  • Isabel Fuentes-Calvo
  • Juan F. Macías Núñez
  • José M. López-Novoa


Adenosine (ADO) is an intermediary metabolite of adenosine trisphosphate degradation and a vasoactive mediator. We showed previously that ADO induces contraction and proliferation in rat mesangial cells by a mechanism involving A1 and A2 receptors. The studies concerning the effect of ADO on extracellular matrix (ECM) accumulation in mesangial cells are scarce. The purpose of our study was to evaluate the effect of ADO and the effect of the selective stimulation of A1 and A2 ADO receptors on the expression of ECM components fibronectin and collagen type I, in human and rat renal mesangial cells. Cultured human and rat renal mesangial cells were subjected to selective stimulation of A1 and A2 ADO receptors for 24 and 48 h. Fibronectin and collagen type I expression was evaluated by Western blot; total collagen synthesis was measured by [3H]-proline incorporation into collagen proteins. ADO, A1 and A2 receptor stimulation induce increases in fibronectin expression in rat mesangial cells, and A1 receptor stimulation partially inhibits fibronectin expression in serum-stimulated rat mesangial cells, without any effect in human mesangial cells. A2 receptor stimulation reduces collagen type I expression in serum-stimulated mesangial cells. Neither ADO nor A1 or A2 receptor stimulation induce significant changes in total collagen synthesis. These data suggest that ADO is not a major regulator of ECM synthesis in rat and human mesangial cells.


Adenosine Collagen Extracellular matrix Fibronectin Fibrosis Mesangial cells Kidney 



This study was supported by grants from Instituto de Salud Carlos III (Ministerio de Sanidad y Consumo, CP03/00094, PI041817, and C03/10), Comisión Interministerial de Ciencia y Tecnología (BFU-2004-00285/BFI), and Junta de Castilla y León (SA001C05 y SA32/04). Immortalized human mesangial cells were a kind gift of Dr. Bernard Banas (Klinik und Poliklinik für Innere Medizin II, University of Regensburg, Regensburg, Germany)


  1. 1.
    Jackson EK, Zacharia LC, Zhang M et al (2006) cAMP-adenosine pathway in the proximal tubule. J Pharmacol Exp Ther 317:1219–1229PubMedCrossRefGoogle Scholar
  2. 2.
    Vallon V, Muhlbauer B, Osswald H (2006) Adenosine and kidney function. Physiol Rev 86:901–940PubMedCrossRefGoogle Scholar
  3. 3.
    Macias-Nunez JF, Garcia-Iglesias C, Santos JC et al (1985) Influence of plasma renin content, intrarenal angiotensin II, captopril, and calcium channel blockers on the vasoconstriction and renin release promoted by adenosine in the kidney. J Lab Clin Med 106:562–567PubMedGoogle Scholar
  4. 4.
    Hansen PB, Hashimoto S, Oppermann M et al (2005) Vasoconstrictor and vasodilator effects of adenosine in the mouse kidney due to preferential activation of A1 or A2 adenosine receptors. J Pharmacol Exp Ther 315:1150–1157PubMedCrossRefGoogle Scholar
  5. 5.
    Palmer TM, Stiles GL (1995) Adenosine receptors. Neuropharmacology 34:683–694PubMedCrossRefGoogle Scholar
  6. 6.
    Arend LJ, Haramati A, Thompson CI et al (1984) Adenosine-induced decrease in renin release: disociation from hemodynamic effects. Am J Physiol 247:F447–F452PubMedGoogle Scholar
  7. 7.
    Huang DY, Vallon V, Zimmermann H et al (2006) Ecto-5′-nucleotidase (cd73)-dependent and -independent generation of adenosine participates in the mediation of tubuloglomerular feedback in vivo. Am J Physiol 291:282–288CrossRefGoogle Scholar
  8. 8.
    Persson PB, Hansell P, Liss P (2005) Pathophysiology of contrast medium-induced nephropathy. Kidney Int 68:14–22PubMedCrossRefGoogle Scholar
  9. 9.
    Mene P, Simonson MJ, Dunn MS (1989) Physiology of the mesangium. Physiol Rev 64:1347–1370Google Scholar
  10. 10.
    Schnaper HW, Hayashida T, Hubchak SC et al (2003) TGF-beta signal transduction and mesangial cell fibrogenesis. Am J Physiol 284:F243–F252Google Scholar
  11. 11.
    Lopez-Novoa JM, de Arriba G, Barrio V et al (1987) Adenosine induces a calcium-dependent glomerular contraction. Eur J Pharmacol 134:365–367PubMedCrossRefGoogle Scholar
  12. 12.
    Olivera A, Lamas S, Rodriguez-Puyol D et al (1989) Adenosine induces mesangial cell contraction by an A1-type receptor. Kidney Int 35:1300–1305PubMedCrossRefGoogle Scholar
  13. 13.
    Olivera A, Lopez-Rivas A, Lopez-Novoa JM (1992) Adenosine stimulates Ca2+ fluxes and increases cytosolic free Ca2+ in cultured rat mesangial cells. Biochem J 282:871–876PubMedGoogle Scholar
  14. 14.
    MacLaughlin M, Martinez-Salgado C, Eleno N et al (1997) Adenosine activates mesangial cell proliferation. Cell Signal 9:59–63PubMedCrossRefGoogle Scholar
  15. 15.
    Zhao Z, Kapoian T, Shepard M et al (2002) Adenosine-induced apoptosis in glomerular mesangial cells. Kidney Int 61:1276–1285PubMedCrossRefGoogle Scholar
  16. 16.
    Banas B, Luckow B, Moller M et al (1999) Chemokine and chemokine receptor expression in a novel human mesangial cell line. J Am Soc Nephrol 10:2314–2322PubMedGoogle Scholar
  17. 17.
    Rodriguez-Barbero A, Dorado F, Velasco S et al (2006) TGF-beta1 induces COX-2 expression and PGE2 synthesis through MAPK and PI3K pathways in human mesangial cells. Kidney Int 70:901–909PubMedCrossRefGoogle Scholar
  18. 18.
    Rodríguez-Puyol D, Lamas S, Olivera A et al (1989) Action of cyclosporin A on cultured rat mesangial cells. Kidney Int 35:632–637PubMedCrossRefGoogle Scholar
  19. 19.
    Martinez-Salgado C, Rodriguez-Barbero A, Rodriguez-Puyol D et al (1997) Involvement of phospholipase A2 in gentamicin-induced rat mesangial cell activation. Am J Physiol 273:F60–F66PubMedGoogle Scholar
  20. 20.
    Martínez-Salgado C, Eleno N, Tavares P et al (2002) Involvement of reactive oxygen species on gentamicin-induced mesangial cell activation. Kidney Int 62:1672–1692CrossRefGoogle Scholar
  21. 21.
    Martínez-Salgado C, Fuentes-Calvo I, García-Cenador B et al (2006) Involvement of H- and N-Ras isoforms in transforming growth factor-β1-induced proliferation and in collagen and fibronectin synthesis. Exp Cell Res 312:2093–2106PubMedCrossRefGoogle Scholar
  22. 22.
    Brown RD, Thoren P, Steege A et al (2005) The influence of the adenosine A1-receptor on blood pressure regulation and renin release. Am J Physiol 290:R1324–R1329Google Scholar
  23. 23.
    Osswald H, Muhlbauer B, Vallon V (1997) Adenosine and tubuloglomerular feedback. Blood Purif 15:243–252PubMedCrossRefGoogle Scholar
  24. 24.
    Freissmuth M, Hausleithner V, Tuisl E et al (1987) Glomeruli and microvessels of the rabbit kidney contain both A1- and A2-adenosine receptors. Naunyn Schmiedebergs Arch Pharmacol 335:438–444PubMedCrossRefGoogle Scholar
  25. 25.
    Olivera A, Tomas M, Lopez-Novoa JM (1992) Effect of adenosine A1 and A2 agonists and antagonists on cAMP and Ca2+ in cultured rat mesangial cells. Am J Physiol 262:C840–C844PubMedGoogle Scholar
  26. 26.
    Olivera A, Lopez-Novoa JM (1992) Effect of adenosine and adenosine analogues on cyclic AMP accumulation in cultured mesangial cells and isolated glomeruli of the rat. Br J Pharmacol 107:341–346PubMedGoogle Scholar
  27. 27.
    Awad AS, Huang L, Ye H et al (2006) Adenosine A2A receptor activation attenuates inflammation and injury in diabetic nephropathy. Am J Physiol 290:F828–F837Google Scholar
  28. 28.
    Lange-Sperandio B, Forbes MS, Thornhill B et al (2005) A2A adenosine receptor agonist and PDE4 inhibition delays inflammation but fails to reduce injury in experimental obstructive nephropathy. Nephron Exp Nephrol 100:113–123CrossRefGoogle Scholar
  29. 29.
    Dubey RK, Gillespie DG, Mi Z et al (2005) Adenosine inhibits PDGF-induced growth of human glomerular mesangial cells via A(2B) receptors. Hypertension 46:628–634PubMedCrossRefGoogle Scholar
  30. 30.
    Dubey RK, Gillespie DG, Jackson EK (1998) Adenosine inhibits collagen and protein synthesis in cardiac fibroblasts: role of A2B receptors. Hypertension 31:943–948PubMedGoogle Scholar
  31. 31.
    Dubey RK, Gillespie DG, Jackson EK (1999) Adenosine inhibits collagen and total protein synthesis in vascular smooth muscle cells. Hypertension 33:190–194PubMedGoogle Scholar
  32. 32.
    Biaggioni I (2004) Clinical and molecular pharmacologic characteristics of adenosine-induced vasodilation. Clin Pharmacol Ther 75:137–139PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Carlos Martínez-Salgado
    • 1
  • Begoña García-Cenador
    • 2
  • Isabel Fuentes-Calvo
    • 2
  • Juan F. Macías Núñez
    • 3
  • José M. López-Novoa
    • 2
  1. 1.Unidad de InvestigaciónHospital Universitario de SalamancaSalamancaSpain
  2. 2.Departamento de Fisiología y Farmacología, Instituto “Reina Sofía” de Investigación NefrológicaUniversidad de SalamancaSalamancaSpain
  3. 3.Servicio de Nefrología, Hospital Universitario de SalamancaSalamancaSpain

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