TRPV6 Is a Ca2+ Entry Channel Essential for Ca2+-induced Differentiation of Human Keratinocytes - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Journal of Biological Chemistry Année : 2007

TRPV6 Is a Ca2+ Entry Channel Essential for Ca2+-induced Differentiation of Human Keratinocytes

Résumé

Ca(2+) is an essential factor inducing keratinocyte differentiation due to the natural Ca(2+) gradient in the skin. However, the membrane mechanisms that mediate calcium entry and trigger keratinocyte differentiation had not previously been elucidated. In this study we demonstrate that Ca(2+)-induced differentiation up-regulates both mRNA and protein expression of a transient receptor potential highly Ca(2+)-selective channel, TRPV6. The latter mediates Ca(2+) uptake and accounts for the basal [Ca(2+)](i) in human keratinocytes. Our results show that TRPV6 is a prerequisite for keratinocyte entry into differentiation, because the silencing of TRPV6 in human primary keratinocytes led to the development of impaired differentiated phenotype triggered by Ca(2+). The expression of such differentiation markers as involucrin, transglutaminase-1, and cytokeratin-10 was significantly inhibited by small interfering RNA-TRPV6 as compared with differentiated control cells. TRPV6 silencing affected cell morphology and the development of intercellular contacts, as well as the ability of cells to stratify. 1,25-Dihydroxyvitamin D3, a cofactor of differentiation, dose-dependently increased TRPV6 mRNA and protein expression in human keratinocytes. This TRPV6 up-regulation led to a significant increase in Ca(2+) uptake in both undifferentiated and differentiated keratinocytes. We conclude that TRPV6 mediates, at least in part, the pro-differentiating effects of 1,25-dihydroxyvitamin D3 by increasing Ca(2+) entry, thereby promoting differentiation. Taken together, these data suggest that the TRPV6 channel is a key element in Ca(2+)/1,25-dihydroxyvitamin D3-induced differentiation of human keratinocytes.

Dates et versions

hal-04122829 , version 1 (08-06-2023)

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Citer

V'Yacheslav Lehen’kyi, Benjamin Beck, Renata Polakowska, Maria Charveron, Pascal Bordat, et al.. TRPV6 Is a Ca2+ Entry Channel Essential for Ca2+-induced Differentiation of Human Keratinocytes. Journal of Biological Chemistry, 2007, 282 (31), pp.22582-22591. ⟨10.1074/jbc.M611398200⟩. ⟨hal-04122829⟩

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