纤维化
癌症研究
医学
磷酸化
化学
转化生长因子
激酶
CTGF公司
SMAD公司
蛋白激酶B
作者
Dong Zeng,Zheng Xiao,Qianqian Xu,Hanwen Luo,Lu Wen,Chengyuan Tang,Yi Shan,Jiao Tian,Ju Wei,Ying Li
出处
期刊:Life Sciences
[Elsevier]
日期:2020-11-01
卷期号:260: 118488-118488
被引量:4
标识
DOI:10.1016/j.lfs.2020.118488
摘要
Abstract Aims This study investigated the role and mechanism of action of tumor necrosis factor-like weak inducer of apoptosis (TWEAK) in the pathogenesis of renal interstitial fibrosis (RIF), and its involvement in the anti-RIF effect of norcantharidin (NCTD). Main methods Mice with unilateral ureteral obstruction and BUMPT mouse proximal tubular cells exposed to transforming growth factor (TGF)-β1 were used as in vivo and in vitro models of RIF, respectively. NCTD was administered to mice by intraperitoneal injection (0.075 mg kg−1·day−1). Hematoxylin–eosin and Masson's trichrome staining were performed to assess pathologic changes in the kidney. Immunohistochemistry, western blotting, and real-time PCR were performed to evaluate the expression of TWEAK and the fibrotic factors fibronectin (FN) and collagen type I (Col-I). The role of TWEAK in RIF and in the anti-RIF effect of NCTD was evaluated by TWEAK overexpression and neutralization with a specific antibody, and specific inhibitor of Mothers against decapentaplegic homolog (Smad)3 (SIS3) was used to examine the involvement of TGF-β1/Smad3 signaling. Key findings TWEAK was mainly expressed in renal tubules in mice; the level was markedly elevated in both in vivo and in vitro RIF models. TWEAK overexpression in BUMPT cells increased the levels of phosphorylated Smad3, FN, and Col-I, which were reduced by treatment with SIS3. NCTD suppressed FN and Col-I expression by blocking TWEAK-mediated Smad3 phosphorylation. Significance Upregulation of TWEAK contributes to RIF by promoting Smad3 phosphorylation, while NCTD inhibits this process.
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