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Deprecated: Implicit conversion from float 276.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Mediators+Inflamm 2016 ; 2016 (ä): ä Nephropedia Template TP
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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-?1 Signaling Pathway #MMPMID27365897
Liu Z; Xue L; Liu Z; Huang J; Wen J; Hu J; Bo L; Yang R
Mediators Inflamm 2016[]; 2016 (ä): ä PMID27365897show ga
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-?1, p-p38 MAPK, p-Smad2, COL-1, and ?-SMA proteins. In vitro, hTWEAK treatment upregulated the expressions of TGF-?1, p-p38 MAPK, p-SMAD2, ?-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-?1 signaling pathway, and phosphorylation of Smad2 and p38 MAPK proteins was also involved in this signaling pathway.