title: Tumor Necrosis Factor-Like Weak Inducer of Apoptosis Accelerates the Progression of Renal Fibrosis in Lupus Nephritis by Activating SMAD and p38 MAPK in TGF-β1 Signaling Pathway.
abstract: This study aim was to explore the effects of tumor necrosis factor-like weak inducer of apoptosis (TWEAK) in lupus nephritis and its potential underlying mechanisms. MRL/lpr mice were used for in vivo experiments and human proximal tubular cells (HK2 cells) were used for in vitro experiments. Results showed that MRL/lpr mice treated with vehicle solution or LV-Control shRNA displayed significant proteinuria and severe renal histopathological changes. LV-TWEAK-shRNA treatment reversed these changes and decreased renal expressions of TWEAK, TGF-β1, p-p38 MAPK, p-Smad2, COL-1, and α-SMA proteins. In vitro, hTWEAK treatment upregulated the expressions of TGF-β1, p-p38 MAPK, p-SMAD2, α-SMA, and COL-1 proteins in HK2 cells and downregulated the expressions of E-cadherin protein, which were reversed by cotreatment with anti-TWEAK mAb or SB431542 treatment. These findings suggest that TWEAK may contribute to chronic renal changes and renal fibrosis by activating TGF-β1 signaling pathway, and phosphorylation of Smad2 and p38 MAPK proteins was also involved in this signaling pathway.
authors.affiliation: Department of Biological Science & Engineering, Hebei University of Science & Technology, Shijiazhuang 050018, China.
authors.forename: Zhiqin
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Rheumatology and Immunology, The Second Affiliated Hospital of Soochow University, Suzhou 215000, China.
authors.forename: Leixi
authors.initials: L
authors.lastname: Xue
authors.affiliation: Department of Rheumatology and Immunology, The Second Affiliated Hospital of Soochow University, Suzhou 215000, China.
authors.forename: Zhichun
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Rheumatology and Immunology, The Second Affiliated Hospital of Soochow University, Suzhou 215000, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Rheumatology and Immunology, The Second Affiliated Hospital of Soochow University, Suzhou 215000, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wen
authors.affiliation: Department of Rheumatology and Immunology, The Second Affiliated Hospital of Soochow University, Suzhou 215000, China.
authors.forename: Ji
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Rheumatology and Immunology, The Second Affiliated Hospital of Soochow University, Suzhou 215000, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Bo
authors.affiliation: Department of Rheumatology and Immunology, The Second Affiliated Hospital of Soochow University, Suzhou 215000, China.
authors.forename: Ru
authors.initials: R
authors.lastname: Yang
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D015820:Cadherins / Q000378:metabolism; D002460:Cell Line; D000074049:Cytokine TWEAK; D004149:Dioxoles / Q000494:pharmacology; D005260:Female; D006801:Humans; D008181:Lupus Nephritis / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D051899:Smad2 Protein / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D000079424:Tumor Necrosis Factor Inhibitors; D048069:Tumor Necrosis Factors / Q000235:genetics / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: C459179:4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide; C541116:ACTA2 protein, human; D000199:Actins; D001549:Benzamides; D015820:Cadherins; D000074049:Cytokine TWEAK; D004149:Dioxoles; D034741:RNA, Small Interfering; D051899:Smad2 Protein; C109743:TNFSF12 protein, human; C491645:Tnfsf12 protein, mouse; D053773:Transforming Growth Factor beta1; D000079424:Tumor Necrosis Factor Inhibitors; D048069:Tumor Necrosis Factors; C544013:alpha-smooth muscle actin, mouse; D048051:p38 Mitogen-Activated Protein Kinases