title: Abietic acid inhibits UVB-induced MMP-1 expression in human dermal fibroblast cells through PPARα/γ dual activation.
abstract: Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily of ligand-activated transcription factors and consist of three isotypes: PPARα, PPARβ/δ and PPARγ. PPARs are expressed in various cell types in the skin, including keratinocytes, fibroblasts and infiltrating immune cells. Thus, these receptors are highly studied in dermato-endocrine research, and their ligands are targets for the treatment of various skin disorders, such as photoageing and chronological ageing of skin. Intensive studies have revealed that PPARα/γ functions in photoageing and age-related inflammation by regulating matrix metalloproteinases (MMPs) via nuclear factor-kappa B (NF-κB) and activator protein-1 (AP-1). However, the detailed mechanism of PPARα/γ's role in photoageing has not yet been elucidated. In this study, we confirmed that abietic acid (AA) is a PPARα/γ dual ligand and significantly decreased UVB-induced MMP-1 expression by downregulating UVB-induced MAPK signalling and downstream transcription factors, subsequently reducing IκBα degradation and blocking NF-κB p65 nuclear translocation in Hs68 human dermal fibroblast cells. Treatment of cells with AA and GW6471 or bisphenol A diglycidyl ether (BADGE), PPARα or PPARγ antagonists, respectively, reversed the effect on UVB-induced MMP-1 expression and inflammatory signalling pathway activation. Taken together, our data suggest that AA acts as a PPARα/γ dual activator to inhibit UVB-induced MMP-1 expression and age-related inflammation by suppressing NF-κB and the MAPK/AP-1 pathway and can be a useful agent for improving skin photoageing.
authors.affiliation: Natural Skinomics Team, KIST Gangneung Institute of Natural Products, Gangneung, Korea.
authors.forename: Youngsic
authors.initials: Y
authors.lastname: Jeon
authors.forename: Yujung
authors.initials: Y
authors.lastname: Jung
authors.forename: Jong-Kyung
authors.initials: JK
authors.lastname: Youm
authors.forename: Ki Sung
authors.initials: KS
authors.lastname: Kang
authors.forename: Yong Kee
authors.initials: YK
authors.lastname: Kim
authors.forename: Su-Nam
authors.initials: SN
authors.lastname: Kim
mesh_terms: D045784:Abietanes / Q000737:chemistry*; D021581:Active Transport, Cell Nucleus; D002460:Cell Line; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D007249:Inflammation; D008024:Ligands; D008027:Light; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism*; D047493:PPAR alpha / Q000378:metabolism*; D047495:PPAR gamma / Q000378:metabolism*; D015398:Signal Transduction; D012867:Skin / Q000187:drug effects / Q000378:metabolism*; D015595:Skin Aging; D012879:Skin Physiological Phenomena; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D051996:Transcription Factor RelA / Q000378:metabolism; D014466:Ultraviolet Rays
chemical_list: D045784:Abietanes; D008024:Ligands; D047493:PPAR alpha; D047495:PPAR gamma; C498143:RELA protein, human; D018808:Transcription Factor AP-1; D051996:Transcription Factor RelA; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1; C023710:abietic acid
keywords: AP-1; MMPs; NF-κB; PPARα/γ dual activator; abietic acid