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KS0365, a novel activator of the transient receptor potential vanilloid 3 (TRPV3) channel, accelerates keratinocyte migration. | LitMetric

AI Article Synopsis

Article Abstract

Background And Purpose: Ca signalling mediated by the thermosensitive, non-selective, Ca -permeable transient receptor potential channel TRPV3 is assumed to play a critical role in regulating several aspects of skin functions, such as keratinocyte proliferation, differentiation, skin barrier formation and wound healing. Studying the function of TRPV3 in skin homeostasis, however, is still constrained by a lack of potent and selective pharmacological modulators of TRPV3.

Experimental Approach: By screening an in-house compound library using fluorometric intracellular Ca assays, we identified two chemically related hits. The more potent and efficient TRPV3 activator 2-(2-chloro-3-isopropylcyclopent-2-en-1-yl)-4-methylphenol (KS0365) was further evaluated in fluo-4-assisted Ca assays, different Ca imaging approaches, electrophysiological studies, cytotoxicity and migration assays.

Key Results: KS0365 activated recombinant and native mouse TRPV3 more potently and with a higher efficacy compared with 2-APB and did not activate TRPV2 or TRPV4 channels. The activation of TRPV3 by KS0365 super-additively accelerated the EGF-induced keratinocyte migration, which was inhibited by the TRP channel blocker ruthenium red or by siRNA-mediated TRPV3 knockdown. Moreover, KS0365 induced strong Ca responses in migrating front cells and in leading edges of keratinocytes.

Conclusions And Implications: The selective TRPV3 activator KS0365 triggers increases in [Ca ] with most prominent signals in the leading edge and accelerates migration of keratinocytes. TRPV3 activators may promote re-epithelialization upon skin wounding.

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Source
http://dx.doi.org/10.1111/bph.15937DOI Listing

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