A novel role for the TRPV1 channel in UV‐induced matrix metalloproteinase (MMP)‐1 expression in HaCaT cells

Abstract

Transient receptor potential vanilloid type 1 (TRPV1) is a molecular sensor for detecting adverse stimuli, such as capsaicin, heat, and acid. TRPV1 has been localized in keratinocytes and is suggested to be a mediator of heat-induced matrix metalloproteinase-1 (MMP-1). With regard to the multimodal activation of TRPV1, we hypothesize that TRPV1 might also mediate UV-induced MMP-1 in keratinocytes. In HaCaT, a human keratinocyte cell line, we initially confirmed capsaicin-induced membrane current and Ca(2+) influx. UV irradiation induced slow and persistent calcium influx and increased membrane current, which was inhibited by TRPV1 inhibitors (capsazepine and ruthenium red). The UV-induced MMP-1 expression in HaCaT was also decreased by TRPV1 inhibitors and was facilitated by capsaicin. Knock-down of TRPV1 using siRNA transfection also decreased MMP-1 expression, as well as UV-induced Ca(2+) influx in HaCaT. UV failed to induce MMP-1 expression in HaCaT cells cultured in Ca(2+)-free media. Both the UV-induced increase in [Ca(2+)](i) and MMP-1 were suppressed by Gö6976 (a calcium-dependent PKC inhibitor), but not by rottlerin (a calcium-independent PKC inhibitor). In addition to a plausible role of TRPV1 in UV-induced MMP-1 expression, we showed that UV increased TRPV1 expression in both HaCaT cells and human skin in vivo. From these results, we suggest that UV-induced MMP-1 expression might be mediated in part by PKC-dependent activation of TRPV1 and subsequent Ca(2+)-influx in human keratinocytes. J. Cell. Physiol. 219: 766-775, 2009. (c) 2009 Wiley-Liss, Inc.

Effects of Bambusae Caulis in Taeniam Extract on the UVB-induced Cell Death, Oxidative Stress and Matrix Metalloproteinase 1 Expression in Keratinocytes

“…The protective effects of p-CA against the UV-induced inflammatory responses or injury has been previously observed in cells and in vivo models [32][33][34]. We suppose that p-CA is one of the active constituents of BCTE based on the observations in the current study, but other studies reported that BCTE contained various other constituents with antioxidant properties [16,17]. Thus, the activity of BCTE can be attributed to the multiple constituents rather than any single compound.…”

“…These MMPs can regulate connective tissue remodeling leading to the formation of wrinkles, and other phenotypes of photoaged skin [14,15]. MMP1 secreted not only from dermal fibroblasts and but from epidermal keratinocytes is known to participate in collagen destruction in the skin [16,17].…”

Cocarcinogenic Effect of Capsaicin Involves Activation of EGFR Signaling but Not TRPV1

“…In skin, TRPV1 is also expressed in keratinocytes and fibroblasts (28). TRPV1 activation is involved in inflammatory responses in human keratinocytes through the release of inflammatory mediators, such as prostaglandin E 2 and interleukin-8 (28), and UV irradiation-increased MMP-1 is mediated by TRPV1 in keratinocytes (29). In contrast, keratinocytes were reportedly resistant to vanilloid-induced TRPV1 activation and subsequent calcium influx (30).…”

TRP Channels and Pruritus

“…Likewise, TRPV1 influenced (i) synthesis of numerous pro-inflammatory mediators produced by human hair follicles [223]; (ii) cytokine and lipid production of human sebaceous gland-derived sebocytes [227]; and (iii) maturation of dendritic cells [225,234]. Furthermore, TRPV1 was found to decrease proliferation, increase apoptosis [226], and induce matrix metalloproteinase production [237][238][239] of epidermal keratinocytes; these effects may all contribute to skin aging and altered barrier functions and hence to the development of related pruritus [237,240]. In good agreement with these data, activation of TRPV1 delayed the barrier recovery after mechanical injury (tape stripping) which effect was blocked by capsazepine, a TRPV1 antagonist [241].…”