title: Activation of TGF-β1 by AQP3-Mediated H2O2Transport into Fibroblasts of a Bleomycin-Induced Mouse Model of Scleroderma.
abstract: Hydrogen peroxide (H2O2), the most important reactive oxygen species, mediates intracellular signal transmission and is transported into cells by aquaporin 3 (AQP3). However, it remains unclear whether AQP3 is involved in the pathogenesis of scleroderma. In this study, we examined the role of AQP3 in a bleomycin-induced mouse model of scleroderma. We observed that H2O2and AQP3 levels in mouse skin increased with the bleomycin injection period relative to phosphate-buffered saline-injected control mice. AQP3 mRNA and protein levels were higher in bleomycin mice fibroblasts than in phosphate-buffered saline mice fibroblasts, and AQP3 immunofluorescence signals in the cytoplasm and cell membrane of bleomycin mice fibroblasts were much stronger than those in phosphate-buffered saline mice fibroblasts. Bleomycin-induced increases in H2O2, transforming growth factor-β1, collagen type I, and collagen type III levels in bleomycin mice fibroblasts were blocked by silencing AQP3. In addition, silencing AQP3 decreased H2O2levels, transforming growth factor-β1 expression, and fibrosis in the scleroderma mouse model. These results demonstrate that AQP3-mediated transport of H2O2into bleomycin mice fibroblasts activated transforming growth factor-β1, and silencing AQP3 is a potential approach for treating scleroderma.
authors.affiliation: Department of Dermatology, Tongji Hospital, Tongji University School of Medicine, Shanghai, China; Department of Dermatology, Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, China.
authors.forename: Jingying
authors.initials: J
authors.lastname: Luo
authors.affiliation: Tumor Research Institute of Yunnan Province, The Third Affiliated Hospital of Kunming Medical College, Kunming, Yunnan, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.affiliation: Translational Center for Stem Cell Research, Tongji Hospital, Stem Cell Research Center, Tongji University School of Medicine, Shanghai, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Dermatology, Tongji Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Jiang
authors.affiliation: Department of Respiration, Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Luo
authors.affiliation: Department of Dermatology, Tongji Hospital, Tongji University School of Medicine, Shanghai, China. Electronic address: zhaojingjun2015@aliyun.com.
authors.forename: Jingjun
authors.initials: J
authors.lastname: Zhao
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001692:Biological Transport; D001707:Biopsy, Needle; D001761:Bleomycin / Q000494:pharmacology*; D015153:Blotting, Western; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000378:metabolism*; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D011897:Random Allocation; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D012594:Scleroderma, Localized / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
chemical_list: D053773:Transforming Growth Factor beta1; D001761:Bleomycin; D006861:Hydrogen Peroxide