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Baicalein inhibits matrix metalloproteinase 1 expression via activation of TRPV1-Ca-ERK pathway in ultraviolet B-irradiated human dermal fibroblasts.
- Source :
-
Experimental dermatology [Exp Dermatol] 2019 May; Vol. 28 (5), pp. 568-575. Date of Electronic Publication: 2019 Mar 21. - Publication Year :
- 2019
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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 <superscript>2+</superscript> 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 <superscript>2+</superscript> 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 <superscript>2+</superscript> sensitive. Increased MMP-1 expression was blocked by PD98059, but not by SP600125. Thus, increased MMP-1 expression is mediated by increased cytosolic Ca <superscript>2+</superscript> and ERK phosphorylation. UVB irradiation-induced ROS generation is also Ca <superscript>2+</superscript> sensitive, and UVB irradiation-induced apoptosis is caused by increased ROS. Thus, baicalein, by blocking the UVB irradiation-induced cytosolic Ca <superscript>2+</superscript> 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.<br /> (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
- Subjects :
- Anthracenes pharmacology
Antioxidants metabolism
Antioxidants pharmacology
Apoptosis
Arachidonate 12-Lipoxygenase metabolism
Calcium metabolism
Capsaicin analogs & derivatives
Capsaicin pharmacology
Cytosol metabolism
Dermis cytology
Dermis radiation effects
Egtazic Acid analogs & derivatives
Egtazic Acid pharmacology
Extracellular Signal-Regulated MAP Kinases metabolism
Fibroblasts enzymology
Humans
Leukotrienes metabolism
NF-E2-Related Factor 2 metabolism
Phosphorylation
Reactive Oxygen Species metabolism
Skin Aging
TRPV Cation Channels metabolism
Fibroblasts radiation effects
Flavanones pharmacology
Matrix Metalloproteinase 1 metabolism
Signal Transduction
Skin radiation effects
Ultraviolet Rays
Subjects
Details
- Language :
- English
- ISSN :
- 1600-0625
- Volume :
- 28
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Experimental dermatology
- Publication Type :
- Academic Journal
- Accession number :
- 30825334
- Full Text :
- https://doi.org/10.1111/exd.13912