title: Trans-Zeatin inhibits UVB-induced matrix metalloproteinase-1 expression via MAP kinase signaling in human skin fibroblasts.
abstract: Ultraviolet (UV) irradiation induces the expression of matrix metalloproteinases (MMPs), disturbing the metabolism of extracellular matrix (ECM), and causes the characteristic changes of photoaging in skin. Inhibition of induction of MMPs is suggested to alleviate photoaging induced by UV irradiation. Zeatin, purified from Zea mays, is a member of the cytokinin group of plant growth factors, the activity of which is attributed to its more stable trans form. In this study, we investigated the effect of trans-Zeatin on UVB-induced matrix metalloproteinase-1 (MMP-1) expression in cultured human skin fibroblasts (HSFs) and studied the mechanisms of its actions. We found that pretreatment with trans-Zeatin significantly inhibits UVB-induced MMP-1 expression and c-Jun activation in a dose-dependent manner. We also observed that trans-Zeatin inhibits UVB-induced phosphorylation of ERK, JNK and p38 MAP kinases (MAPKs) dose-dependently. As expected, PD98059, an ERK inhibitor, SP600125, a JNK inhibitor and SB203580, a p38 MAPK inhibitor effectively inhibit UVB-induced phosphorylation of ERK, JNK and p38 MAPKs, respectively. Moreover, the inhibitory mechanism of trans-Zeatin was further demonstrated in MMP-1 secretion using MAPK-specific inhibitors. PD98059, SP600125 and SB203580 suppressed UVB-induced MMP-1 secretion, which is consistent with the above results. Collectively, our results suggest that trans-Zeatin inhibits UVB-induced MMP-1 expression, which may be mediated by inhibition of ERK, JNK and p38 MAPKs signaling pathways in HSFs. Trans-Zeatin is a potential agent for the management of skin photoaging.
authors.affiliation: Jiangsu Province Key Laboratory of Molecular Immunopathology, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, PR China.
authors.forename: Bo
authors.initials: B
authors.lastname: Yang
authors.forename: Chao
authors.initials: C
authors.lastname: Ji
authors.forename: Jian
authors.initials: J
authors.lastname: Kang
authors.forename: Wenqi
authors.initials: W
authors.lastname: Chen
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Bi
authors.forename: Yinsheng
authors.initials: Y
authors.lastname: Wan
mesh_terms: D000873:Anthracenes / Q000494:pharmacology; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007231:Infant, Newborn; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000528:radiation effects; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D010937:Plant Growth Regulators / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D012867:Skin / Q000166:cytology; D014466:Ultraviolet Rays; D015026:Zeatin / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000873:Anthracenes; D004791:Enzyme Inhibitors; D005419:Flavonoids; D007093:Imidazoles; D010937:Plant Growth Regulators; D011725:Pyridines; C432165:pyrazolanthrone; D015026:Zeatin; D020928:Mitogen-Activated Protein Kinases; D020781:Matrix Metalloproteinase 1; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one