BACKGROUND Renal fibrosis is the characteristic of all kinds of chronic kidney diseases (CKDs). Fascin-1 plays an important role in tumor development, but the roles of fascin-1 in renal fibrosis have not been studied. Here, we explored the role of fascin-1 in renal fibrosis and the potential mechanisms. METHODS Kidney unilateral ureteral obstruction (UUO) mouse model was used as an in vivo model, and proximal tubule epithelial cell lines treated with TGF-β1 were used as in vitro model of renal fibrosis. Cell transfection was performed to manipulate the expression of miR-200b/c, fascin-1 and CD44. Western blotting, qRT-PCR, immunohistochemistry or immunofluorescence assays were used to measure levels of miR-200b/c, fascin-1, CD44, and fibrosis and EMT-related markers. H&E and Masson stainings were used to examine the degree of injury and fibrosis in kidneys. Dual luciferase assay was used to examine the interaction between miR-200b/c family and fascin-1. RESULTS Fascin-1 and CD44 levels were both significantly up-regulated while miR-200b/c family was reduced in models of renal fibrosis. Furthermore, overexpression of miR-200b/c family and inhibition of fascin-1 or CD44 ameliorated renal fibrosis through suppressing EMT process. Mechanistically, miR-200b/c family directly and negatively regulated the expression of fascin-1. Overexpression of fascin-1 could reverse the effects of miR-200b/c family on renal fibrosis, and fascin-1 regulated renal fibrosis by activating CD44. CONCLUSION Our study is the first to show that fascin-1 plays a critical role in renal fibrosis. MiR-200b/c family could inhibit renal fibrosis through modulating EMT process by directly targeting fascin-1/CD44 axis.

中文翻译：

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MiR-200b / c家族通过靶向fascin-1 / CD44轴调节上皮向间充质转化，从而抑制了肾纤维化。

背景技术肾纤维化是各种慢性肾脏疾病（CKD）的特征。Fascin-1在肿瘤发展中起重要作用，但是尚未研究fascin-1在肾纤维化中的作用。在这里，我们探讨了fascin-1在肾纤维化中的作用及其潜在机制。方法以肾脏单侧输尿管梗阻（UUO）小鼠模型为体内模型，以TGF-β1处理的近端肾小管上皮细胞系作为肾纤维化的体外模型。进行细胞转染以操纵miR-200b / c，fascin-1和CD44的表达。Western印迹，qRT-PCR，免疫组化或免疫荧光测定法用于测量miR-200b / c，fascin-1，CD44，纤维化和EMT相关标志物的水平。H＆E和Masson染色用于检查肾脏的损伤程度和纤维化程度。使用双重荧光素酶测定法检查miR-200b / c家族与fascin-1之间的相互作用。结果在肾纤维化模型中，Fascin-1和CD44水平均显着上调，而miR-200b / c家族则降低。此外，miR-200b / c家族的过表达和fascin-1或CD44的抑制通过抑制EMT过程改善了肾纤维化。从机制上讲，miR-200b / c家族直接和负调控fascin-1的表达。fascin-1的过度表达可以逆转miR-200b / c家族对肾纤维化的作用，而fascin-1可以通过激活CD44来调节肾纤维化。结论我们的研究首次表明fascin-1在肾纤维化中起关键作用。