Therapeutic role of miR-26a on cardiorenal injury in a mice model of angiotensin-II induced chronic kidney disease through inhibition of LIMS1/ILK pathway  

作　　者：Weijie Ni Yajie Zhao Jinxin Shen Qing Yin Yao Wang Zuolin Li Taotao Tang Yi Wen Yilin Zhang Wei Jiang Liangyunzi Jiang Jinxuan Wei Weihua Gan Aiqing Zhang Xiaoyu Zhou Bin Wang Bi-Cheng Liu 

机构地区：[1]Institute of Nephrology,Zhong Da Hospital,Southeast University School of Medicine,Nanjing,Jiangsu 210003,China [2]Department of Pediatric Nephrology,the Second Affiliated Hospital of Nanjing Medical University,Nanjing,Jiangsu 210003,China [3]Department of Neonates,Children’s Hospital of Nanjing Medical University,Nanjing,Jiangsu 210008,China [4]Department of Nephrology,The Affiliated Hospital of Yangzhou University,Yangzhou,Jiangsu 225100,China

出　　处：《Chinese Medical Journal》2025年第2期193-204,共12页中华医学杂志(英文版)

基　　金：supported by grants from the National Natural Science Foundation of China(Nos.82200749,82241047,82070735,82030024,81720108007 and 81270725);Natural Science Foundation of Jiangsu Province(No.BK20221282);National Key Research Programme of Ministry of Science and Technology(Nos.2018YFC130046,2018YFC1314000).

摘　　要：Background:Chronic kidney disease(CKD)is associated with common pathophysiological processes,such as inflammation and fibrosis,in both the heart and the kidney.However,the underlying molecular mechanisms that drive these processes are not yet fully understood.Therefore,this study focused on the molecular mechanism of heart and kidney injury in CKD.Methods:We generated an microRNA(miR)-26a knockout(KO)mouse model to investigate the role of miR-26a in angiotensin(Ang)-II-induced cardiac and renal injury.We performed Ang-II modeling in wild type(WT)mice and miR-26a KO mice,with six mice in each group.In addition,Ang-II-treated AC16 cells and HK2 cells were used as in vitro models of cardiac and renal injury in the context of CKD.Histological staining,immunohistochemistry,quantitative real-time polymerase chain reaction(PCR),and Western blotting were applied to study the regulation of miR-26a on Ang-II-induced cardiac and renal injury.Immunofluorescence reporter assays were used to detect downstream genes of miR-26a,and immunoprecipitation was employed to identify the interacting protein of LIM and senescent cell antigen-like domain 1(LIMS1).We also used an adeno-associated virus(AAV)to supplement LIMS1 and explored the specific regulatory mechanism of miR-26a on Ang-II-induced cardiac and renal injury.Dunnett’s multiple comparison and t-test were used to analyze the data.Results:Compared with the control mice,miR-26a expression was significantly downregulated in both the kidney and the heart after Ang-II infusion.Our study identified LIMS1 as a novel target gene of miR-26a in both heart and kidney tissues.Downregulation of miR-26a activated the LIMS1/integrin-linked kinase(ILK)signaling pathway in the heart and kidney,which represents a common molecular mechanism underlying inflammation and fibrosis in heart and kidney tissues during CKD.Furthermore,knockout of miR-26a worsened inflammation and fibrosis in the heart and kidney by inhibiting the LIMS1/ILK signaling pathway;on the contrary,supplementation with exoge

关 键 词：microRNA-26a Chronic kidney disease LIMS1 protein Cardiorenal injury INFLAMMATION FIBROSIS 

分 类 号：R692[医药卫生—泌尿科学]