title: Tiron Inhibits UVB-Induced AP-1 Binding Sites Transcriptional Activation on MMP-1 and MMP-3 Promoters by MAPK Signaling Pathway in Human Dermal Fibroblasts.
abstract: Recent research found that Tiron was an effective antioxidant that could act as the intracellular reactive oxygen species (ROS) scavenger or alleviate the acute toxic metal overload in vivo. In this study, we investigated the inhibitory effect of Tiron on matrix metalloproteinase (MMP)-1 and MMP-3 expression in human dermal fibroblast cells. Western blot and ELISA analysis revealed that Tiron inhibited ultraviolet B (UVB)-induced protein expression of MMP-1 and MMP-3. Real-time quantitative PCR confirmed that Tiron could inhibit UVB-induced mRNA expression of MMP-1 and MMP-3. Furthermore, Tiron significantly blocked UVB-induced activation of the MAPK signaling pathway and activator protein (AP)-1 in the downstream of this transduction pathway in fibroblasts. Through the AP-1 binding site mutation, it was found that Tiron could inhibit AP-1-induced upregulation of MMP-1 and MMP-3 expression through blocking AP-1 binding to the AP-1 binding sites in the MMP-1 and MMP-3 promoter region. In conclusion, Tiron may be a novel antioxidant for preventing and treating skin photoaging UV-induced.
authors.affiliation: Institute of Oncology, Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Lu
authors.affiliation: Institute of Oncology, Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Jia-Hui
authors.initials: JH
authors.lastname: Guo
authors.affiliation: Yellow River Hospital Attached Henan University of Science and Technology, Sanmeixia, China.
authors.forename: Xue-Liang
authors.initials: XL
authors.lastname: Tu
authors.affiliation: Institute of Oncology, Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Reproductive Medicine, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Department of pathology, Zhengzhou central hospital affiliated to Zhengzhou University, Zhengzhou, China.
authors.forename: Quan-Wu
authors.initials: QW
authors.lastname: Zhang
authors.affiliation: Institute of Oncology, Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Feng-Hou
authors.initials: FH
authors.lastname: Gao
mesh_terms: D014013:1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D001665:Binding Sites / Q000528:radiation effects; D002478:Cells, Cultured; D019610:Cytoprotection / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects; D020405:Dermis / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000528:radiation effects; D020781:Matrix Metalloproteinase 1 / Q000235:genetics* / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000528:radiation effects; D015398:Signal Transduction / Q000187:drug effects / Q000528:radiation effects; D015595:Skin Aging / Q000187:drug effects / Q000528:radiation effects; D018808:Transcription Factor AP-1 / Q000378:metabolism / Q000528:radiation effects; D015533:Transcriptional Activation / Q000187:drug effects / Q000528:radiation effects; D014466:Ultraviolet Rays / Q000009:adverse effects
chemical_list: D000975:Antioxidants; D018808:Transcription Factor AP-1; D014013:1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt; C511768:MMP3 protein, human; D019278:Matrix Metalloproteinase 3; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1