微小RNA-92b通过靶向I型受体作为转化生长因子-β信号的负调节因子。
MircroRNA-92b as a negative regulator of the TGF-β signaling by targeting the type I receptor.
作者信息
Yang Shu, Jiang Kewei, Li Lixing, Xiang Jiaqing, Li Yanchun, Kang Lin, Yang Guangyan, Liang Zhen
机构信息
Department of Geriatrics, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518000, China.
Guangdong Provincial Clinical Research Center for Geriatrics，Shenzhen Clinical Research Center for Geriatrics, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, 518000 China.
出版信息
iScience. 2023 Oct 5;26(11):108131. doi: 10.1016/j.isci.2023.108131. eCollection 2023 Nov 17.
Transforming growth factor β1 (TGFβ1) has been identified as a major pathogenic factor underlying the development of chronic kidney disease (CKD). This study investigated the role of miR-92b-3p in the progression of renal fibrosis in unilateral ureteral occlusion (UUO) and unilateral ischemia-reperfusion injury (uIRI) mouse models, as well as explored its underlying mechanisms in human proximal tubular epithelial (HK2) cells. We found that renal fibrosis increased in UUO mice after miR-92b knockout, while it reduced in miR-92b overexpressing mice. MiR-92b knockout aggravated renal fibrosis in uIRI mice. RNA-sequencing analysis, the luciferase reporter assay, qPCR analysis, and western blotting confirmed that miR-92b-3p directly targeted TGF-β receptor 1, thereby ameliorating renal fibrosis by suppressing the TGF-β signaling pathway. Furthermore, we found that TGF-β suppressed miR-92b transcription through Snail family transcriptional repressors 1 and 2. Our results suggest that miR-92b-3p may serve as a novel therapeutic for mitigating fibrosis in CKD.
转化生长因子β1（TGFβ1）已被确定为慢性肾脏病（CKD）发展的主要致病因素。本研究调查了miR-92b-3p在单侧输尿管梗阻（UUO）和单侧缺血再灌注损伤（uIRI）小鼠模型肾纤维化进展中的作用，并探讨了其在人近端肾小管上皮（HK2）细胞中的潜在机制。我们发现，miR-92b基因敲除后UUO小鼠的肾纤维化增加，而miR-92b过表达小鼠的肾纤维化减少。miR-92b基因敲除加重了uIRI小鼠的肾纤维化。RNA测序分析、荧光素酶报告基因检测、qPCR分析和蛋白质印迹证实，miR-92b-3p直接靶向TGF-β受体1，从而通过抑制TGF-β信号通路改善肾纤维化。此外，我们发现TGF-β通过Snail家族转录抑制因子1和2抑制miR-92b的转录。我们的结果表明，miR-92b-3p可能作为一种减轻CKD纤维化的新型治疗方法。
Zotero 插件