Heat-induced MMP-1 expression is mediated by TRPV1 through PKCalpha signaling in HaCaT cells

Cited 36 time in Web of Science Cited 39 time in Scopus

Lee, Young Mee; Li, Wen Hai; Kim, Yeon Kyung; Kim, Kyu Han; Chung, Jin Ho

Issue Date
Exp Dermatol. 2008; 17(10): 864-870
Calcium/metabolismCell Line, TransformedExtracellular Signal-Regulated MAP Kinases/metabolismHeat-Shock Response/physiologyHot TemperatureHumansImmunohistochemistryKeratinocytes/cytology/*enzymologyMatrix Metalloproteinase 1/*metabolismProtein Kinase C-alpha/*metabolismSignal Transduction/*physiologyTRPV Cation Channels/*metabolism
BACKGROUND: Matrix metalloproteinase-1 (MMP-1) is considered a key initiator of collagen degradation in inflammatory responses. A heat-gated channel, transient receptor potential vanilloid type 1 (TRPV1), induces release of proinflammatory mediators. TRPV1 channels have been localized to the epidermis and we have recently suggested that they act as mediators of heat-induced MMP-1. The aim of this study was to investigate the signaling of TRPV1 in MMP-1 regulation by heat shock in human epidermal keratinocytes. METHODS: Heat shock-induced MMP-1 expression was decreased by treatment with TRPV1 inhibitor. The heat-induced MMP-1 expression was suppressed by Go6976 [calcium-dependent inhibitor] and staurosporine (ST, broad-spectrum PKC inhibitor), while rottlerin (ROT, calcium-independent PKCdelta inhibitor) had no effect. Also, transfection of PKCalpha siRNA decreased MMP-1 expression, whereas MMP-1 expression was not significantly affected in cells transfected with negative control siRNA, PKCbeta siRNA or PKCdelta siRNA. RESULTS: We demonstrated that heat shock failed to induce MMP-1 expression in HaCaT cells cultured in calcium-free media. The heat-induced [Ca(2+)](i) increase was inhibited by Go6976 and ST, but not by ROT. We also found that heat-induced phosphorylation of ERK, JNK and p38 MAPK in HaCaT cells, but capsazepine and ruthenium red had no effect on this activation. In addition to the role of TRPV1 in heat-induced MMP-1 expression, we also found that heat increased TRPV1 proteins in human skin in vivo. CONCLUSIONS: Our results suggest that TRPV1 mediates heat shock-induced MMP-1 expression via calcium-dependent PKCalpha signaling in HaCaT cells.
1600-0625 (Electronic)
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College of Medicine/School of Medicine (의과대학/대학원)Dermatology (피부과학전공)Journal Papers (저널논문_피부과학전공)
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