聚束蛋白
CD44细胞
纤维化
上皮-间质转换
癌症研究
肾
下调和上调
医学
病理
内科学
免疫组织化学
生物
细胞
癌症
转移
生物化学
基因
作者
Hua Fu,Yonghong Gu,Y F Yang,Shan Liao,Guohui Wang
出处
期刊:Life Sciences
[Elsevier]
日期:2020-03-24
卷期号:252: 117589-117589
被引量:27
标识
DOI:10.1016/j.lfs.2020.117589
摘要
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. 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. 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. 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.
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