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Mechanical-stimulation-evoked calcium waves in proliferating and differentiated human keratinocytes

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Abstract

Calcium dynamics in the epidermis play a crucial role in barrier homeostasis and keratinocyte differentiation. We have recently suggested that the electro-physiological responses of the keratinocyte represent the frontier of the skin sensory system for environmental stimuli. In the present study, we have evaluated the responses of proliferating and differentiated human keratinocytes to mechanical stress by measuring the intracellular calcium level. Before differentiation, mechanical stress induces a calcium wave over a limited area; this is completely blocked by apyrase, which degrades ATP. In the case of differentiated keratinocytes, the calcium wave propagates over a larger area. Application of apyrase does not completely inhibit this wave. Thus, in differentiated cells, the induction of calcium waves might involve not only ATP, but also another factor. Immunohistochemical studies indicate that connexins 26 and 43, both components of gap junctions, are expressed in the cell membrane of differentiated keratinocytes. Application of octanol or carbenxolone, which block gap junctions, significantly reduces calcium wave propagation in differentiated keratinocytes. Thus, signaling via gap junctions might be involved in the induction of calcium waves in response to mechanical stress at the upper layer of the epidermis.

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References

  • Brandner JM, Houdek P, Husing B, Kaiser C, Moll I (2004) Connexins 26, 30 and 43: differences among spontaneous chronic, and accelerated human wound healing. J Invest Dermatol 122:1310–1320

    Article  CAS  PubMed  Google Scholar 

  • Chateau Y, Dorange G, Clement JF, Pennec JP, Gobin E, Griscom L, Baudrimont M, Rougier N, Chesne C, Misery L (2007) In vitro reconstruction of neuro-epidermal connections. J Invest Dermatol 127:979–981

    Article  CAS  PubMed  Google Scholar 

  • Denda M (2003) Epidermis of the skin as a self-organizing electrochemical sensor. In: Nakata S (ed) Chemical analysis based on nonlinearity. NOVA, New York, pp 132–138

    Google Scholar 

  • Denda M, Sato J, Tsuchiya T, Elias PM, Feingold KR (1998a) Low humidity stimulates epidermal DNA synthesis and amplifies the hyperproliferative response to barrier disruption: implication for seasonal exacerbations of inflammatory dermatoses. J Invest Dermatol 111:873–878

    Article  CAS  Google Scholar 

  • Denda M, Sato J, Masuda Y, Tsuchiya T, Kuramoto M, Elias PM, Feingold KR (1998b) Exposure to a dry environment enhances epidermal permeability barrier function. J Invest Dermatol 111:858–863

    Article  CAS  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Denda M, Fuziwara S, Inoue K, Denda S, Akamatsu H, Tomitaka A, Matsunaga K (2001) Immunoreactivity of VR1 on epidermal keratinocyte of human skin. Biochem Biophys Res Commun 285:1250–1252

    Article  CAS  PubMed  Google Scholar 

  • Denda M, Inoue K, Fuziwara S, Denda S (2002) 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 

  • Denda M, Fuziwara S, Inoue K (2004) Association of cyclic AMP with permeability barrier homeostasis. J Invest Dermatol 122:140–146

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Dhaka A, Viswanath V, Patapoutian A (2006) TRP ion channels and temperature sensation. Annu Rev Neurosci 29:135–161

    Article  CAS  PubMed  Google Scholar 

  • Elias PM, Feingold KR (1992) Lipids and the epidermal water barrier: metabolism, regulation, and pathophysiology. Semin Dermatol 11:176–182

    CAS  PubMed  Google Scholar 

  • Elias PM, Ahn SK, Denda M, Brown BE, Crumrine D, Kimutai LK, Kömüves L, Lee SH, Feingold KR (2002) Modulations in epidermal calcium regulate the expression of differentiation-specific proteins. J Invest Dermatol 119:1128–1136

    Article  CAS  PubMed  Google Scholar 

  • Enomoto K, Furuya K, Yamagishi S, Oka T, Maeno T (1994) The increase in the intracellular Ca2+ concentration induced by mechanical stimulation is propagated via release of pyrophosphorylated nucleotides in mammary epithelial cells. Pflugers Arch 427:533–542

    Article  CAS  PubMed  Google Scholar 

  • Forslind B, Werner-Linde Y, Lindberg M, Pallon J (1999) Elemental analysis mirrors epidermal differentiation. Acta Derm Venereol (Stockh) 79:12–17

    Article  CAS  Google Scholar 

  • Fuziwara S, Suzuki A, Inoue K, Denda M (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 

  • Goldberg GS, Moreno AP, Lampe PD (2002) Gap junctions between cells expressing connexin 43 or 32 show inverse permselectivity to adenosine and ATP. J Biol Chem 277:36725–36730

    Article  CAS  PubMed  Google Scholar 

  • Goldberg GS, Valiunas V, Brink PR (2004) Selective permeability of gap junction channels. Biochim Biophys Acta 1662:96–101

    Article  CAS  PubMed  Google Scholar 

  • Grando SA, Pittelkow MR, Schallreuter KU (2006) Adrenergic and cholinergic control in the biology of epidermis: physiological and clinical significance. J Invest Dermatol 126:1948–1965

    Article  CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Inoue K, Denda M, Tozaki H, Fujishita K, Koizumi S, Inoue K (2005) Characterization of multiple P2X receptors in cultured normal human epidermal keratinocytes. J Invest Dermatol 124:756–763

    Article  CAS  PubMed  Google Scholar 

  • Kandyba EE, Hodgins MB, Martin PE (2008) A murine living skin equivalent amenable to live-cell imaging: analysis of the roles of connexins in the epidermis. J Invest Dermatol 128:1039–1049

    Article  CAS  PubMed  Google Scholar 

  • Koizumi S, Fijishita K, Inoue K, Shigemoto-Mogami Y, Tsuda M, Inoue K (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  CAS  PubMed  Google Scholar 

  • Langlois S, Maher AC, Manias JL, Shao Q, Kidder GM, Laird DW (2007) Connexin levels regulate keratinocyte differentiation in the epidermis. J Biol Chem 282:30171–30180

    Article  CAS  PubMed  Google Scholar 

  • Mauro T, Bench G, Sidderas-Haddad E, Feingold KR, Elias PM, Cullander C (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 

  • Menon GK, Price LF, Bommannan B, Elias OM, Feingold KR (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 

  • Mese G, Richard G, White TW (2007) Gap junctions: basic structure and function. J Invest Dermatol 127:2516–2524

    Article  CAS  PubMed  Google Scholar 

  • Mire P, Nasse J, Venable-Thibodeaux S (2000) Gap junctional communication in the vibration-sensitive response of sea anemones. Hear Res 144:109–123

    Article  CAS  PubMed  Google Scholar 

  • Navarro X, Verdu E, Wendelscafer-Crabb G, Kennedy WR (1995) Innervation of cutaneous structures in the mouse hind paw: a confocal microscopy immunohistochemical study. J Neurosci Res 41:111–120

    Article  CAS  PubMed  Google Scholar 

  • Nishizaki T (2004) ATP- and adenosine-mediated signaling in the central nervous system: adenosine stimulates glutamate release from astrocytes via A2a adenosine receptors. J Pharmacol Sci 94:100–102

    Article  CAS  PubMed  Google Scholar 

  • Proksch E, Feingold KR, Man MQ, Elias PM (1991) Barrier function regulates epidermal DNA synthesis. J Clin Invest 87:1668–1673

    Article  CAS  PubMed  Google Scholar 

  • Salomon D, Masgrau E, Vischer S, Ullrich S, Dupont E, Sappino P, Saurat JH, Meda P (1994) Topography of mammalian connexins in human skin. J Invest Dermatol 103:240–247

    Article  CAS  PubMed  Google Scholar 

  • Tang EHC, Vanhoutte PM (2008) Gap junction inhibitors reduce endothelium-dependent contraction in the aorta of spontaneously hypertensive rats. J Pharmacol Exp Ther 327:148–153

    Article  CAS  PubMed  Google Scholar 

  • Tsutsumi M, Denda S, Inoue K, Ikeyama K, Denda M (2009) Calcium ion gradients and dynamics in cultured skin slices of rat hind-paw in response to stimulation with ATP. J Invest Dermatol 129:584–589

    Article  CAS  PubMed  Google Scholar 

  • Yano S, Komine M, Fujimoto M, Okouchi H, Tamaki K (2004) Mechanical stretching in vitro regulates signal transduction pathways and cellular proliferation in human epidermal keratinocytes. J Invest Dermatol 122:783–790

    Article  CAS  PubMed  Google Scholar 

  • Yano S, Komine M, Fujimoto M, Okouchi H, Tamaki K (2006) Activation of Akt by mechanical stretching in human epidermal keratinocytes. Exp Dermatol 15:356–361

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Shiseido Research Center, 2-12-1, Fukuura, Kanazawa-ku, Yokohama, 236-8643, Japan

    Moe Tsutsumi, Kaori Inoue, Sumiko Denda, Kazuyuki Ikeyama, Makiko Goto & Mitsuhiro Denda

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  1. Moe Tsutsumi
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  2. Kaori Inoue
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  3. Sumiko Denda
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  4. Kazuyuki Ikeyama
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  5. Makiko Goto
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  6. Mitsuhiro Denda
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Correspondence to Mitsuhiro Denda.

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Tsutsumi, M., Inoue, K., Denda, S. et al. Mechanical-stimulation-evoked calcium waves in proliferating and differentiated human keratinocytes. Cell Tissue Res 338, 99–106 (2009). https://doi.org/10.1007/s00441-009-0848-0

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  • DOI: https://doi.org/10.1007/s00441-009-0848-0

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