A novel role for the TRPV1 channel in UV-induced matrix metalloproteinase (MMP)-1 expression in HaCaT cells

• Published in: Journal of cellular physiology 2009-06, Vol.219 (3), p.766-775
• Main Authors: Lee, Young Mee, Kim, Yeon Kyung, Kim, Kyu Han, Park, Su Jung, Kim, Sung Joon, Chung, Jin Ho
• Format: Article
• Language: English
• Subjects: Base Sequence; Calcium Signaling - radiation effects; Capsaicin - analogs & derivatives; Capsaicin - pharmacology; Cell Line; DNA, Complementary - genetics; Humans; Keratinocytes - metabolism; Keratinocytes - radiation effects; Matrix Metalloproteinase 1 - genetics; Matrix Metalloproteinase 1 - metabolism; Models, Biological; Protein Kinase C - antagonists & inhibitors; Protein Kinase C - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism; RNA, Small Interfering - genetics; Skin - metabolism; Skin - radiation effects; Skin Aging - physiology; Skin Aging - radiation effects; Transfection; TRPV Cation Channels - agonists; TRPV Cation Channels - antagonists & inhibitors; TRPV Cation Channels - genetics; TRPV Cation Channels - metabolism; Ultraviolet Rays - adverse effects
• ISSN: 0021-9541; 1097-4652
• DOI: 10.1002/jcp.21729

Transient receptor potential vanilloid type 1 (TRPV1) is a molecular sensor for detecting adverse stimuli, such as capsaicin, heat, and acid. TRPV1 has been localized in keratinocytes and is suggested to be a mediator of heat‐induced matrix metalloproteinase‐1 (MMP‐1). With regard to the multimodal activation of TRPV1, we hypothesize that TRPV1 might also mediate UV‐induced MMP‐1 in keratinocytes. In HaCaT, a human keratinocyte cell line, we initially confirmed capsaicin‐induced membrane current and Ca2+ influx. UV irradiation induced slow and persistent calcium influx and increased membrane current, which was inhibited by TRPV1 inhibitors (capsazepine and ruthenium red). The UV‐induced MMP‐1 expression in HaCaT was also decreased by TRPV1 inhibitors and was facilitated by capsaicin. Knock‐down of TRPV1 using siRNA transfection also decreased MMP‐1 expression, as well as UV‐induced Ca2+ influx in HaCaT. UV failed to induce MMP‐1 expression in HaCaT cells cultured in Ca2+‐free media. Both the UV‐induced increase in [Ca2+]i and MMP‐1 were suppressed by Gö6976 (a calcium‐dependent PKC inhibitor), but not by rottlerin (a calcium‐independent PKC inhibitor). In addition to a plausible role of TRPV1 in UV‐induced MMP‐1 expression, we showed that UV increased TRPV1 expression in both HaCaT cells and human skin in vivo. From these results, we suggest that UV‐induced MMP‐1 expression might be mediated in part by PKC‐dependent activation of TRPV1 and subsequent Ca2+‐influx in human keratinocytes. J. Cell. Physiol. 219: 766–775, 2009. © 2009 Wiley‐Liss, Inc.