Baicalein inhibits matrix metalloproteinase 1 expression via activation of TRPV1‐Ca‐ERK pathway in ultraviolet B–irradiated human dermal fibroblasts. Issue 5 (21st March 2019)

• Record Type: Journal Article
• Authors: Huang, Kuo‐Feng; Ma, Kuo‐Hsing; Chang, Yen‐Jung; Lo, Liang‐Chuan; Jhap, Tian‐You; Su, Yu‐Hua; Liu, Pei‐Shan; Chueh, Sheau‐Huei
• Is Part Of: Experimental dermatology. Volume 28:Issue 5(2019)
• Page Start: 568
• Page End: 575
• Publication Date: 2019-03-21
• Subjects: 12‐lipoxygenase -- cytosolic Ca2+ increase -- ERK phosphorylation -- Nrf2 -- reactive oxygen species; Dermatology -- Periodicals; 616.5
• DOI: 10.1111/exd.13912
• Languages: English
• ISSNs: 0906-6705

Abstract

Abstract: Increased matrix metalloproteinase 1 (MMP‐1) expression is a feature of photo‐aged skin. We investigated the effects of baicalein and sulphoraphane on ultraviolet B (UVB) irradiation–induced MMP‐1 expression and apoptosis using human dermal fibroblasts. UVB irradiation not only increased MMP‐1 expression, but also caused apoptosis. Both baicalein and sulphoraphane protected cells from UVB irradiation–induced apoptosis, but only baicalein inhibited MMP‐1 expression. UVB irradiation activated 12‐lipoxygenase, and its product, 12‐hydroxyeicosatetraenoic acid, activated TRPV1 channels. The resulting UVB irradiation–induced Ca 2+ increase was blocked by the 12‐lipoxygenase inhibitor baicalein and the TRPV1 blocker capsazepine, but not by the Nrf2 inducer sulphoraphane. UVB irradiation also increased ROS generation and decreased Nrf2 protein levels. UVB irradiation–induced MMP‐1 expression was blocked by the Ca 2+ chelator BAPTA, by capsazepine and by TRPV1 silencing. However, induction was unaffected by the antioxidant N‐acetylcysteine. ERK phosphorylation and JNK phosphorylation were induced by UVB irradiation, but only ERK phosphorylation was Ca 2+ sensitive. Increased MMP‐1 expression was blocked by PD98059, but not by SP600125. Thus, increased MMP‐1 expression is mediated by increased cytosolic Ca 2+ and ERK phosphorylation. UVB irradiation–induced ROS generation is also Ca 2+ sensitive, and UVB irradiation–induced apoptosis is caused by increased ROS. Thus, baicalein, by blocking the UVB irradiation–induced cytosolic Ca 2+ increase, protects cells from UVB irradiation–induced MMP‐1 expression and apoptosis. In contrast, sulphoraphane, by decreasing cellular ROS, protects cells from only UVB‐induced apoptosis. Thus, targeting 12‐lipoxygenase may provide a therapeutic approach to improving the health of photo‐aged human skin.