Skip to main content
SpringerLink
Log in
Book cover

Transient Receptor Potential Channels pp 847–860Cite as

Roles of Transient Receptor Potential Proteins (TRPs) in Epidermal Keratinocytes

  • Chapter
  • First Online:

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 704))

Abstract

Epidermal keratinocytes are the epithelial cells of mammalian skin. At the basal layer of the epidermis, these cells proliferate strongly, and as they move towards the skin surface, differentiation proceeds. At the uppermost layer of the epidermis, keratinocytes undergo apoptosis and die, forming a thin, water-impermeable layer called the stratum corneum. Peripheral blood vessels do not reach the epidermis, but peripheral nerve fibers do penetrate into it. Until recently, it was considered that the main role of epidermal keratinocytes was to construct and maintain the water-impermeable barrier function. However, since the functional existence of TRPV1, which is activated by heat and low pH, in epidermal keratinocytes was identified, our understanding of the role of keratinocytes has changed enormously. It has been found that many TRP channels are expressed in epidermal keratinocytes, and play important roles in differentiation, proliferation and barrier homeostasis. Moreover, because TRP channels expressed in keratinocytes have the ability to sense a variety of environmental factors, such as temperature, mechanical stress, osmotic stress and chemical stimuli, epidermal keratinocytes might form a key part of the sensory system of the skin. The present review deals with the potential roles of TRP channels expressed in epidermal keratinocytes and focuses on the concept of the epidermis as an active interface between the body and the environment.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Abbreviations

TRP:

transient receptor potential

References

  1. Friel DD (1996) TRP: its role in phototransduction and store-operated Ca2+ entry. Cell 85:617–619

    Article  CAS  PubMed  Google Scholar 

  2. Caterina MJ, Schumacher MA, Tominaga M et al (2007) The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature 389:816–824

    Google Scholar 

  3. Denda M, Fuziwara, Inoue K et al (2001) Immunoreactivity of VR1 on epidermal keratinocyte of human skin. Biochem Biophys Res Commun 285:1250–1252

    Article  CAS  PubMed  Google Scholar 

  4. Inoue K, Koizumi S, Fuziwara S et al (2002) Functional vanilloid receptors in cultured normal human keratinocytes. Biochem Biophys Res Commun 291:124–129

    Article  CAS  PubMed  Google Scholar 

  5. Peier AM, Reeve AJ, Andersson DA, Moqrich A, Earley TJ, Hergarden AC, Story GM, Colley S, Hogenesch JB, McIntyre P, Bevan S, Patapoutian A (2002) A heat-sensitive TRP channel expressed in keratinocytes. Science 296:2046–2049

    Article  CAS  PubMed  Google Scholar 

  6. Chung MK, Lee H, Caterina MJ (2003) Warm temperatures activate TRPV4 in mouse 308 keratinocytes. J Biol Chem 278:32037–32046

    Article  CAS  PubMed  Google Scholar 

  7. Atoyan R, Shander D, Botchkarvera NV (2009) Non-neural expression of transient receptor potential type A1 (TRPA1) in human skin. J Invest Dermatol 129:2096–2099

    Article  Google Scholar 

  8. Story GM, Peier AM, Reeve AJ et al (2003) ANKTM1, a TRP-like channel expressed in nociceptive neurons, is activated by cold temperatures. Cell 112:819–829

    Article  CAS  PubMed  Google Scholar 

  9. Tsutsumi M, Denda S, Ikeyama K et al (2010) Exposure to low temperature induces elevation of intracellular calcium in cultured human keratinocytes. J Invest Dermatol 130:1945–1948

    Article  CAS  PubMed  Google Scholar 

  10. Cai S, Fatherazi S, Presland RB et al (2005) TRPC channel expression during calcium-induced differentiation of human gingival keratinocytes. J Dermatol Sci 40:21–28

    Article  CAS  PubMed  Google Scholar 

  11. Beck B, Lehen’kyi V, Roudbaraki M et al (1998) TRPC channels determine human keratinocyte differentiation: new insight into basal cell carcinoma. Cell Calcium 43:492–505

    Article  Google Scholar 

  12. Mauro T, Bench G, Sidderas-Haddad E et al (1998) Acute barrier perturbation abolishes the Ca2+ and K+ gradients in murine epidermis: quantitative measurement using PIXE. J Invest Dermatol 111:1198–1201

    Article  CAS  PubMed  Google Scholar 

  13. Forslind B, Werner-Linde Y, Lindberg M et al (1999) Elemental analysis mirrors epidermal differentiation. Acta Derm Venereol 79:12–17

    Article  CAS  PubMed  Google Scholar 

  14. Elias PM, Ahn SK, Denda M et al (2002) Modulations in epidermal calcium regulate the expression of differentiation-specific proteins. J Invest Dermatol 119:1128–1136

    Article  CAS  PubMed  Google Scholar 

  15. Watt FM (1989) Terminal differentiation of epidermal keratinocytes. Curr Opin Cell Biol 1:1107–1115

    Article  CAS  PubMed  Google Scholar 

  16. Nemes Z, Steinert PM (1999) Bricks and mortar of the epidermal barrier. Exp Mol Med 31:5–19

    Article  CAS  PubMed  Google Scholar 

  17. Watanabe R, Wu K, Paul P et al (1998) Up-regulation of glucosylceramide synthase expression and activity during human keratinocyte differentiation. J Biol Chem 273:9651–9655

    Article  CAS  PubMed  Google Scholar 

  18. Menon GK, Price LF, Bommannan B et al (1994) Selective obliteration of the epidermal calcium gradient leads to enhanced lamellar body secretion. J Invest Dermatol 102:789–795

    Article  CAS  PubMed  Google Scholar 

  19. Cai S, Fatherazi S, Presland RB et al (2006) Evidence that TRPC1 contributes to calcium-induced differentiation of human keratinocytes. Pflugers Arch 452:43–52

    Article  CAS  PubMed  Google Scholar 

  20. Tu CL, Chang W, Bikle DD (2005) Phospholipase cgamma1 is required for activation of store-operated channels in human keratinocytes. J Invest Dermatol 124:187–197

    Article  CAS  PubMed  Google Scholar 

  21. Müller M, Essin K, Hill K et al (2008) Specific, TRPC6 channel activation, a novel approach to stimulate keratinocyte differentiation. J Biol Chem 283:33942–33954

    Article  PubMed Central  PubMed  Google Scholar 

  22. Woelfle U, Laszczyk MN, Kraus M et al (2010) Triterpenes promote keratinocyte differentiation in vitro, ex vivo and in vivo: a role for the transient receptor potential canonical (subtype) 6. J Invest Dermatol 130:113–123

    Article  CAS  PubMed  Google Scholar 

  23. Huyke C, Reuter J, Rödig M et al (2009) Treatment of actinic keratoses with a novel betulin-based oleogel. A prospective randomized comparative pilot study. J Dtsch Dermatol Ges 7:128–133

    PubMed  Google Scholar 

  24. Lehen’kyi V, Beck B, Polakowska R et al (2007) TRPV6 is a Ca2+ entry channel essential for Ca2+-induced differentiation of human keratinocytes. J Biol Chem 282:22582–22591

    Article  PubMed  Google Scholar 

  25. Bianco SD, Peng JB, Takanaga H, Suzuki Y, Crescenzi A, Kos CH, Zhuang L, Freeman MR, Gouveia CH, Wu J, Luo H, Mauro T, Brown EM, Hediger MA (2007) Marked disturbance of calcium homeostasis in mice with targeted disruption of the Trpv6 calcium channel gene. J Bone Miner Res 22:274–285

    Article  CAS  PubMed  Google Scholar 

  26. Southall MD, Li T, Gharibova LS et al (2003) Activation of epidermal vanilloid receptor-1 induces release of proinflammatory mediators in human keratinocytes. J Pharmacol Exp Ther 304:217–222

    Article  CAS  PubMed  Google Scholar 

  27. Li WH, Lee YM, Kim JY et al (2007) Transient receptor potential vanilloid-1 mediates heat-shock-induced matrix metalloproteinase-1 expression in human epidermal keratinocytes. J Invest Dermatol 127:2328–2335

    Article  CAS  PubMed  Google Scholar 

  28. Denda S, Denda M, Inoue K et al (2010) Glycolic acid induces keratinocyte proliferation in a skin equivalent model via TRPV1 activation. J Dermatol Sci 57:108–113

    Article  CAS  PubMed  Google Scholar 

  29. Lee YM, Kim YK, Chung JH (2009a) Increased expression of TRPV1 channel in intrinsically aged and photoaged human skin in vivo. Exp Dermatol 18:431–436

    Article  CAS  PubMed  Google Scholar 

  30. Lee YM, Kim YK, Kim KH et al (2009b) A novel role for the TRPV1 channel in UV-induced matrix metalloproteinase (MMP)-1 expression in HaCaT cells. J Cell Physiol 219:766–775

    Article  CAS  PubMed  Google Scholar 

  31. Wilder-Smith EP, Ong WY, Guo Y et al (2007) Epidermal transient receptor potential vanilloid 1 in idiopathic small nerve fibre disease, diabetic neuropathy and healthy human subjects. Histopathology 51:674–680

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  32. Yoshioka T, Imura K, Asakawa M et al (2009) Impact of the Gly573Ser substitution in TRPV3 on the development of allergic and pruritic dermatitis in mice. J Invest Dermatol 129: 714–722

    Article  CAS  PubMed  Google Scholar 

  33. Asakawa M, Yoshioka T, Matsutani T et al (2006) Association of a mutation in TRPV3 with defective hair growth in rodents. J Invest Dermatol 126:2664–2672

    Article  CAS  PubMed  Google Scholar 

  34. Katsuta Y, Iida T, Inomata S et al (2005) Unsaturated fatty acids induce calcium influx into keratinocytes and cause abnormal differentiation of epidermis. J Invest Dermatol 124: 1008–1013

    Article  CAS  PubMed  Google Scholar 

  35. Hu HZ, Xiao R, Wang C et al (2006) Potentiation of TRPV3 channel function by unsaturated fatty acids. J Cell Physiol 208:201–212

    Article  CAS  PubMed  Google Scholar 

  36. Pani B, Cornatzer E, Cornatzer W et al (2006) Up-regulation of transient receptor potential canonical 1 (TRPC1) following sarco(endo)plasmic reticulum Ca2+ ATPase 2 gene silencing promotes cell survival: a potential role for TRPC1 in Darier’s disease. Mol Biol Cell 17:4446–4458

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  37. Elias PM, Feingold KR (2001) Coordinate regulation of epidermal differentiation and barrier homeostasis. Skin Pharmacol Appl Skin Physiol 14(Suppl 1):28–34

    Article  CAS  PubMed  Google Scholar 

  38. Denda M, Sokabe T, Tominaga T (2007) Effects of skin surface temperature on epidermal permeability barrier homeostasis. J Invest Dermatol 127:654–659

    Article  CAS  PubMed  Google Scholar 

  39. Grubauer G, Elias PM, Feingold KR (1989) Transepidermal water loss: the signal for recovery of barrier structure and function. J Lipid Res 30:323–333

    CAS  PubMed  Google Scholar 

  40. Liedtke W (2007) Role of TRPV ion channels in sensory transduction of osmotic stimuli in mammals. Exp Physiol 92:507–512

    Article  CAS  PubMed  Google Scholar 

  41. Denda M, Tsutsumi M, Goto M et al (2010) Topical application of TRPA1 agonists and brief cold exposure accelerate skin permeability barrier recovery. J Invest Dermatol 130:1942–1945

    Article  CAS  PubMed  Google Scholar 

  42. Bandell M, Story GM, Hwang SW et al (2004) Noxious cold ion channel TRPA1 is activated by pungent compounds and bradykinin. Neuron 41:849–857

    Article  CAS  PubMed  Google Scholar 

  43. Grice KA (1980) Transepidermal water loss in pathologic skin. In: Jarrett A (ed) The, Physiology and Pathophysiology of the Skin. Academic Press, London, UK, pp 2147–2155

    Google Scholar 

  44. Denda M, Kitamura K, Elias PM, Feingold KR (1997) Trans-4-(aminomethyl)cyclohexane carboxylic acid (t-AMCHA), an anti-fibrinolytic agent, accelerates barrier recovery and prevents the epidermal hyperplasia induced by epidermal injury in hairless mice and humans. J Invest Dermatol 109:84–90

    Article  CAS  PubMed  Google Scholar 

  45. Fuziwara S, Ogawa K, Aso D et al (2004) Barium sulfate with a negative ζ potential accelerates skin permeable barrier recovery and prevents epidermal hyperplasia indueced by barrier disruption. Br J Dermarol 151:557–564

    Article  CAS  Google Scholar 

  46. Bodó E, Bíró T, Telek A et al (2005) A hot new twist to hair biology: involvement of vanilloid receptor-1 (VR1/TRPV1) signaling in human hair growth control. Am J Pathol 166:985–998

    Article  PubMed Central  PubMed  Google Scholar 

  47. Bíró T, Bodó E, Telek A et al (2006) Hair cycle control by vanilloid receptor-1 (TRPV1): evidence from TRPV1 knockout mice. J Invest Dermatol 126:1909–1912

    Article  PubMed  Google Scholar 

  48. Imura K, Yoshioka T, Hikita I et al (2007) Influence of TRPV3 mutation on hair growth cycle in mice. Biochem Biophys Res Commun 363:479–483

    Article  CAS  PubMed  Google Scholar 

  49. Tóth BI, Géczy T, Griger Z et al (2009) Transient receptor potential vanilloid-1 signaling as a regulator of human sebocyte biology. J Invest Dermatol 129:329–339

    Article  PubMed  Google Scholar 

  50. Tominaga M, Caterina MJ, Malmberg AB et al (1998) The cloned capsaicin receptor integrates multiple pain-producing stimuli. Neuron 21:531–543

    Article  CAS  PubMed  Google Scholar 

  51. Xu H, Delling M, Jun JC et al (2006) Oregano, thyme and clove-derived flavors and skin sensitizers activate specific TRP channels. Nat Neurosci 9:628–635

    Article  CAS  PubMed  Google Scholar 

  52. Moqrich A, Hwang SW, Earley TJ et al (2005) Impaired thermosensation in mice lacking TRPV3, a heat and camphor sensor in the skin. Science 307:1468–1472

    Article  CAS  PubMed  Google Scholar 

  53. Becker D, Blase C, Bereiter-Hahn J et al (2005) TRPV4 exhibits a functional role in cell-volume regulation. J Cell Sci 118(Pt 11):2435–2440

    Article  CAS  PubMed  Google Scholar 

  54. Denda M, Sato J, Masuda Y et al (1998) Exposure to a dry environment enhances epidermal permeability barrier function. J Invest Dermatol 111:858–863

    Article  CAS  PubMed  Google Scholar 

  55. Goto M, Ikeyama, Tsutsumi KM et al (2010) Calcium ion propagation in cultured keratinocytes and other cells in skin in response to hydraulic pressure stimulation. J Cell Physiol 224:229–233

    CAS  PubMed  Google Scholar 

  56. Liedtke W (2008) Molecular mechanisms of TRPV4-mediated neural signaling. Ann NY Acad Sci 1144:42–52

    Article  CAS  PubMed  Google Scholar 

  57. Story GM, Gereau RW 4th (2006) Numbing the senses: role of TRPA1 in mechanical and cold sensation. Neuron 50:177–180

    Article  CAS  PubMed  Google Scholar 

  58. Koizumi S, Fijishita K, Inoue K et al (2004) Ca2+ waves in keratinocytes are transmitted to sensory neurons: the involvement of extracellular ATP and P2Y2 receptor activation. Biochem J 380:329–338

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  59. Huang SM, Lee H, Chung MK et al (2008) Overexpressed transient receptor potential vanilloid 3 ion channels in skin keratinocytes modulate pain sensitivity via prostaglandin E2. J Neurosci 28:13727–13737

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  60. Ikeyama K, Fuziwara S, Denda M (1719) Topical application of neuronal nitric oxide synthase inhibitor accelerates cutaneous barrier recovery and prevents epidermal hyperplasia induced by barrier disruption. J Invest Dermatol 2007:127:1713–1719

    Google Scholar 

  61. Fuziwara S, Inoue K, Denda M (2003) NMDA-type glutamate receptor is associated with cutaneous barrier homeostasis. J Invest Dermatol 120:1023–1029

    Article  CAS  PubMed  Google Scholar 

  62. Fuziwara S, Suzuki A, Inoue K et al (2005) Dopamine, D2-like receptor agonists accelerate barrier repair and inhibit the epidermal hyperplasia induced by barrier disruption. J Invest Dermatol 125:783–789

    Article  CAS  PubMed  Google Scholar 

  63. Navarro X, Verdu E, Wendelschafer-Crabb G et al (1995) Innervation of cutaneous structures in the mouse hind paw: a confocal microscopy immmunohistochemical study. J Neurosci Res 41:111–120

    Article  CAS  PubMed  Google Scholar 

  64. Cockayne DA, Hamilton SG, Zhu QM et al (2000) Urinary bladder hyporeflexia and reduced pain-related behavior in P2X3-deficient mice. Nature 407:1011–1015

    Article  CAS  PubMed  Google Scholar 

  65. Tsutsumi M, Ikeyama K, Denda S et al (2009) Expressions of rod and cone photoreceptor-like proteins in human epidermis. Exp Dermatol 18:567–570

    Article  CAS  PubMed  Google Scholar 

  66. Corey DP, García-Añoveros J, Holt JR et al (2004) TRPA1 is a candidate for the mechanosensitive transduction channel of vertebrate hair cells. Nature 432:723–730

    Article  CAS  PubMed  Google Scholar 

  67. Denda M, Nakatani M (2010) Acceleration of permeability barrier recovery by exposure of skin to 10–30 kilohertz sound. Br J Dermatol 162:503–507

    Article  CAS  PubMed  Google Scholar 

  68. Denda M, Inoue K, Fuziwara S et al (2002a) P2X purinergic receptor antagonist accelerates skin barrier repair and prevents epidermal hyperplasia induced by skin barrier disruption. J Invest Dermatol 119:1034–1040

    Article  CAS  PubMed  Google Scholar 

  69. Denda M, Inoue K, Inomata S et al (2002b) GABA (A) receptor agonists accelerate cutaneous barrier recovery and prevent epidermal hyperplasia induced by barrier disruption. J Invest Dermatol 119:1041–1047

    Article  CAS  PubMed  Google Scholar 

  70. Denda M (2003a) Epidermis of the skin as a self-organizing electrochemical sensor. In: Nakata S (eds) Chemical, Analysis Based on Nonlinearity. NOVA, New York, NY, pp 132–138

    Google Scholar 

  71. Denda M, Fuziwara S, Inoue K (2003b) Beta-2-adrenergic receptor antagonist accelerates skin barrier recovery and reduces epidermal hyperplasia induced by barrier disruption. J Invest Dermatol 121:142–148

    Article  CAS  PubMed  Google Scholar 

  72. Ikeyama K, Denda S, Tsutsumi M et al (2010) Neuronal nitric oxide synthase in epidermis is involved in cutaneous circulatory response to mechanical stimulation. J Invest Dermatol 130:1158–1166

    Article  CAS  PubMed  Google Scholar 

  73. Zanello SB, Jackson DM, Holick MF (1999) An immunocytochemical approach to the study of beta-endorphin production in human keratinocytes using confocal microscopy. Ann N Y Acad Sci 885:85–99

    Article  CAS  PubMed  Google Scholar 

  74. Seike M, Ikeda M, Morimoto A et al (2002) Increased synthesis of calcitonin gene-related peptide stimulates keratinocyte proliferation in murine UVB-irradiated skin. J Dermatol Sci 28:135–143

    Article  CAS  PubMed  Google Scholar 

  75. Bae S, Matsunaga Y, Tanaka Y et al (1999) Autocrine induction of substance P mRNA and peptide in cultured normal human keratinocytes. Biochem Biophys Res Commun 263: 327–333

    Article  CAS  PubMed  Google Scholar 

  76. Chung MK, Lee H, Mizuno A et al (2004) TRPV3 and TRPV4 mediate warmth-evoked currents in primary mouse keratinocytes. J Biol Chem 279:21569–21575

    Article  CAS  PubMed  Google Scholar 

  77. Denda M (2000a) Influence of dry environment on epidermal function. J Dermatol Sci 24(Suppl 1):S22–S28

    Article  CAS  PubMed  Google Scholar 

  78. Denda M, Hosoi J, Ashida Y (2000b) Visual imaging of ion distribution in human epidermis. Biochem Biophys Res Commun 272:134–137

    Article  CAS  PubMed  Google Scholar 

  79. Denda M, Fuziwara S, Inoue K (2003c) Influx of calcium and chloride ions into epidermal keratinocytes regulates exocytosis of epidermal lamellar bodies and skin permeability barrier homeostasis. J Invest Dermatol 121:362–367

    Article  CAS  PubMed  Google Scholar 

  80. Denda M, Nakatani M, Ikeyama K et al (2007a) Epidermal keratinocytes as the forefront of the sensory system. Exp Dermatol 16:157–161

    Article  CAS  PubMed  Google Scholar 

  81. Denda M, Fuziwara S (2008) Visible radiation affects epidermal permeability barrier recovery: selective effects of red and blue light. J Invest Dermatol 128:1335–1336

    Article  CAS  PubMed  Google Scholar 

  82. Denda M, Fuziwara S, Inoue K (2004) Association of cyclic adenosine monophosphate with permeability barrier homeostasis of murine skin. J Invest Dermatol 122:140–146

    Article  CAS  PubMed  Google Scholar 

  83. Denda M, Tsutsumi M, Denda S (2010) Topical application of TRPM8 agonists accelerates skin permeability barrier recovery and reduces epidermal proliferation induced by barrier insult: Therde of cold-sensitive TRP receptors in epidermal permeability barrier homeostasis. Exp Dermatol 19:791–795

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Shiseido Research Center, Yokohama, Kanagawa, 236-8643, Japan

    Mitsuhiro Denda & Moe Tsutsumi

Authors
  1. Mitsuhiro Denda
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Moe Tsutsumi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mitsuhiro Denda .

Editor information

Editors and Affiliations

  1. Dept. Clinical Research & Education, Södersjukhuset, Karolinska Institutet, Stockholm, 118 83, Sweden

    Md. Shahidul Islam

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer Science+Business Media B.V.

About this chapter

Cite this chapter

Denda, M., Tsutsumi, M. (2011). Roles of Transient Receptor Potential Proteins (TRPs) in Epidermal Keratinocytes. In: Islam, M. (eds) Transient Receptor Potential Channels. Advances in Experimental Medicine and Biology, vol 704. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-0265-3_44

Download citation

Publish with us

Policies and ethics

Search

Navigation