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Lefty-1 inhibits renal epithelial-mesenchymal transition by antagonizing the TGF-β/Smad signaling pathway.
Journal of Molecular Histology ( IF 2.9 ) Pub Date : 2020-02-17 , DOI: 10.1007/s10735-020-09859-8
Lijun Zhang 1 , Xiaohua Liu 1 , Jun Liang 1 , Jianhua Wu 1 , Daqing Tan 1 , Wei Hu 2
Affiliation  

Epithelial–mesenchymal transition (EMT) is a biological process in which tubular epithelial cells lose their phenotypes, and new mesenchymal feature are obtained. In particular, type II EMT possibly contributes to renal tissue fibrogenesis. Recent studies indicate that Lefty-1, a novel member of the TGF-β superfamily with pleiotropical and biological regulation characteristics on TGF-β and other signaling pathways, is considered to have potential fibrotic effects. However, its role in EMT, which is often a long-term consequence of renal tubulointerstitial fibrosis, remains unknown. In this study, we found that Lefty-1 alleviates EMT induction through antagonizing TGF-β/Smad pathway in vivo and in vitro. In unilateral ureteral obstruction (UUO) model mice, administration of adenovirus-mediated overexpression of Lefty-1 (Ad-Lefty-1) significantly reduced TGF-β1/Smad expression and alleviated the phenotypic transition of epithelial cells to mesenchymal cells and extracellular matrix (ECM) accumulation. In high glucose-induced rat renal tubular duct epithelial cell line (NRK-52E), EMT and ECM synthesis were alleviated with Lefty-1 treatment, which significantly inhibited TGF-β1/Smad pathway activation in UUO mice and high glucose-treated NRK-52E cells. Thus, Lefty-1 can alleviate EMT and renal interstitial fibrosis in vivo and in vitro through antagonizing the TGF-β/Smad pathway, and Lefty-1 might have a potential novel therapeutic effect on fibrotic kidney diseases.

中文翻译:

Lefty-1通过拮抗TGF-β/ Smad信号通路抑制肾脏上皮-间质转化。

上皮-间质转化(EMT)是一种生物学过程,其中肾小管上皮细胞失去其表型,并获得了新的间充质特征。特别地,II型EMT可能有助于肾组织纤维发生。最近的研究表明,Lefty-1是TGF-β超家族的新型成员,对TGF-β和其他信号通路具有多效性和生物学调节特性,被认为具有潜在的纤维化作用。然而,其在EMT中的作用(通常是肾小管间质纤维化的长期结果)仍然未知。在这项研究中,我们发现Lefty-1通过在体内和体外拮抗TGF-β/ Smad途径来减轻EMT诱导。在单侧输尿管阻塞(UUO)模型小鼠中,腺病毒介导的Lefty-1(Ad-Lefty-1)的过量表达可显着降低TGF-β1/ Smad的表达,并减轻上皮细胞向间充质细胞的表型转变和细胞外基质(ECM)的积累。在高糖诱导的大鼠肾小管上皮细胞系(NRK-52E)中,Lefty-1处理可减轻EMT和ECM的合成,从而显着抑制UUO小鼠和高糖处理的NRK-T小鼠的TGF-β1/ Smad途径活化。 52E细胞。因此,Lefty-1可通过拮抗TGF-β/ Smad途径在体内和体外减轻EMT和肾脏间质纤维化,Lefty-1可能对纤维化性肾脏疾病具有潜在的新型治疗作用。
更新日期:2020-02-17
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