title: Oxymatrine inhibits renal fibrosis of obstructive nephropathy by downregulating the TGF-β1-Smad3 pathway.
abstract: This study investigated whether oxymatrine (OMT) treatment can ameliorate renal interstitial fibrosis in unilateral ureteral obstruction (UUO) mice model. Moreover, the potential mechanisms of such treatment were analyzed. Twenty-four C57/BL6 mice were randomly divided into three groups, namely sham group, vehicle plus unilateral ureteral obstruction (UUO)-treated group, and 100 mg/kg/d OMT plus UUO-treated group. All mice were euthanized seven days after surgery, and their kidneys were harvested. Renal injury, fibrosis, expression of proinflammatory cytokines, and the transforming growth factor-β1/Smads (TGF-β/Smads) and nuclear factor-kappa B (NF-κB)-signaling pathways were assessed. The results showed OMT significantly prevented kidney injury and fibrosis, as evidenced by decreased expression of collagen-1 and fibronectin. Furthermore, OMT administration inhibited the release of inflammatory factors including tumor necrosis factor-α, (TNF-α) interleukin-1β (IL-1β), and interleukin-6 (IL-6), as well as phosphorylated NF-κB p65. In addition, OMT blocked the activation of myofibroblasts by inhibiting the TGF-β/Smad3-signaling pathway. The findings indicate that OMT-attenuated renal fibrosis and inflammation, and this renoprotective effect may be ascribed to the inactivation of the TGF-β/Smad3 and NF-κB p65 pathways.
authors.affiliation: a Department of Cardiology , People's Hospital of Xianfeng County , Xianfeng , China ;
authors.forename: Hong-Wei
authors.initials: HW
authors.lastname: Wang
authors.affiliation: b Department of Oncology , Renmin Hospital of Wuhan University , Wuhan , China ;
authors.forename: Lei
authors.initials: L
authors.lastname: Shi
authors.affiliation: c Department of Scientific Research Office , Renmin Hospital of Wuhan University , Wuhan , China ;
authors.forename: Yan-Ping
authors.initials: YP
authors.lastname: Xu
authors.affiliation: d Department of Orthopedics , People's Hospital of Xianfeng County , Xianfeng , China ;
authors.forename: Xing-Ya
authors.initials: XY
authors.lastname: Qin
authors.affiliation: e Department of Gastroenterology , People's Hospital of Xianfeng County , Xianfeng , China.
authors.forename: Qi-Zhi
authors.initials: QZ
authors.lastname: Wang
mesh_terms: D058186:Acute Kidney Injury / Q000517:prevention & control; D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D015536:Down-Regulation; D005355:Fibrosis / Q000517:prevention & control; D007249:Inflammation / Q000188:drug therapy; D007668:Kidney / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011807:Quinolizines / Q000494:pharmacology*; D011897:Random Allocation; D015398:Signal Transduction / Q000187:drug effects*; D051900:Smad3 Protein / Q000378:metabolism*; D051996:Transcription Factor RelA / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D014517:Ureteral Obstruction / Q000473:pathology; D000093842:Matrines
chemical_list: D000470:Alkaloids; D016207:Cytokines; D011807:Quinolizines; D051900:Smad3 Protein; D051996:Transcription Factor RelA; D053773:Transforming Growth Factor beta1; C498144:Rela protein, mouse; C497791:Smad3 protein, mouse; C508961:Tgfb1 protein, mouse; C037573:oxymatrine; D000093842:Matrines
keywords: Inflammation; TGF-β/Smad3; kidney fibrosis; oxymatrine