title: Transient receptor potential vanilloid-1 mediates heat-shock-induced matrix metalloproteinase-1 expression in human epidermal keratinocytes.
abstract: Transient receptor potential vanilloid-1 (TRPV1), a heat-gated channel, was recently found on human keratinocytes and the activation of epidermal TRPV1 was known to induce release of proinflammatory mediators. However, the functional consequences of TRPV1 activation in cutaneous physiology and pathology have not been elucidated clearly. In this study, we investigated the role of TRPV1 on the matrix metalloproteinase (MMP)-1 expression induced by heat shock in human epidermal keratinocytes. Heat shock induced the expression of MMP-1 mRNA and protein in a temperature-dependent manner in an immortalized human keratinocyte cell line (HaCaT) and normal human epidermal keratinocytes (NHK). Heat-shock-induced MMP-1 expression was decreased by treatment of the TRPV1 inhibitors (capsazepine and ruthenium red) or knockdown of TRPV1 using RNA interference in HaCaT cells. Overexpression of TRPV1 greatly increased heat-shock-induced MMP-1 promoter activity in HEK 293 cells. Furthermore, direct activation of TRPV1 by capsaicin, a TRPV1 agonist, increased MMP-1 expression. We found that heat shock induced calcium influx through TRPV1 and that extracellular calcium was necessary for heat-shock-induced MMP-1 expression in HaCaT cells. Taken together, our results suggest that heat-shock-induced MMP-1 expression is mediated by activation of TRPV1 and is dependent on a calcium-dependent signaling process in human epidermal keratinocytes.
authors.affiliation: Department of Dermatology, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Wen H
authors.initials: WH
authors.lastname: Li
authors.forename: Young M
authors.initials: YM
authors.lastname: Lee
authors.forename: Jee Y
authors.initials: JY
authors.lastname: Kim
authors.forename: Seokwon
authors.initials: S
authors.lastname: Kang
authors.forename: Sangmin
authors.initials: S
authors.lastname: Kim
authors.forename: Kyu H
authors.initials: KH
authors.lastname: Kim
authors.forename: Chi-Hyun
authors.initials: CH
authors.lastname: Park
authors.forename: Jin H
authors.initials: JH
authors.lastname: Chung
mesh_terms: D020013:Calcium Signaling / Q000502:physiology; D002211:Capsaicin / Q000031:analogs & derivatives / Q000494:pharmacology; D002460:Cell Line; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006358:Hot Temperature; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism* / Q000473:pathology; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D012430:Ruthenium Red / Q000494:pharmacology; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D034741:RNA, Small Interfering; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; D012430:Ruthenium Red; D020781:Matrix Metalloproteinase 1; C071423:capsazepine; D002211:Capsaicin