Transient receptor potential vanilloid-1 mediates heat-shock-induced matrix metalloproteinase-1 expression in human epidermal keratinocytes

J Invest Dermatol. 2007 Oct;127(10):2328-35. doi: 10.1038/sj.jid.5700880. Epub 2007 May 17.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcium Signaling / physiology
  • Capsaicin / analogs & derivatives
  • Capsaicin / pharmacology
  • Cell Line
  • Cells, Cultured
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / physiology
  • Hot Temperature
  • Humans
  • Keratinocytes / metabolism*
  • Keratinocytes / pathology
  • Male
  • Matrix Metalloproteinase 1 / genetics
  • Matrix Metalloproteinase 1 / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Small Interfering / pharmacology
  • Ruthenium Red / pharmacology
  • TRPV Cation Channels / antagonists & inhibitors
  • TRPV Cation Channels / genetics
  • TRPV Cation Channels / metabolism*


  • RNA, Messenger
  • RNA, Small Interfering
  • TRPV Cation Channels
  • TRPV1 protein, human
  • Ruthenium Red
  • Matrix Metalloproteinase 1
  • capsazepine
  • Capsaicin