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.

Epidermal keratinocyte polarity and motility require Ca2+ influx through TRPV1

“…We found that inhibition of TRPV1, but not TRPV4 or TRPM7, impaired keratinocyte polarity and migration. TRPV1 expression has been defined mostly in sensory ganglia (dorsal root, trigeminal and nodose) (Caterina et al, 2000), although it has also been detected in epithelial cells of the bladder lumen (Birder et al, 2002), epidermal keratinocytes (Denda et al, 2001;Pecze et al, 2008), as well as other non-neuronal tissue (Southall et al, 2003;Li et al, 2007). We detected robust levels of trpv1 in trigeminal sensory neurons in 24-hour embryos, which is consistent with its well-documented role in neuronal sensory function.…”

Upregulation of Transient Receptor Potential Vanilloid Type-1 Channel Activity and Ca2+Influx Dysfunction in Human Pterygial Cells

“…17 Transient receptor potential V1 mediates heat shock-induced matrix metalloproteinase-1 (MMP-1) expression in human keratinocytes. 18 However, diverse TRPV1 activation mechanisms induced through various (physical) stimuli have not yet iovs.arvojournals.org j ISSN: 1552-5783 been elucidated. High-resolution analysis of TRPV1 structure identified conformational changes in an outer pore domain and lower gate domain through ligand-binding.…”

Progress of Pruritus Research in Atopic Dermatitis

“…These results suggested that interaction between keratinocytes and sensory nerves is involved in itch response and diverse receptors and targets on keratinocytes might be candidates for controlling the itch of atopic dermatitis. These views might be supported by the existence of targets, such as TRPV1 and TP receptors, on keratinocytes (Peier et al, 2002;Li et al, 2007;Andoh, 2008).…”