MircroRNA-92b as a negative regulator of the TGF-β signaling by targeting the type I receptor

被引:0
作者
Yang, Shu [1 ,2 ,3 ,4 ]
Jiang, Kewei [1 ,2 ,3 ,4 ]
Li, Lixing [1 ,2 ,3 ,4 ]
Xiang, Jiaqing [1 ,2 ,3 ,4 ]
Li, Yanchun [1 ,2 ,3 ,4 ]
Kang, Lin [1 ,2 ,3 ,4 ,5 ]
Yang, Guangyan [1 ,2 ,3 ,4 ]
Liang, Zhen [1 ,2 ,3 ,4 ]
机构
[1] Jinan Univ, Shenzhen Peoples Hosp, Dept Geriatr, Clin Med Coll 2, Guangzhou, Peoples R China
[2] Southern Univ Sci & Technol, Affiliated Hosp 1, Shenzhen 518000, Peoples R China
[3] Jinan Univ, Shenzhen Peoples Hosp, Guangdong Prov Clin Res Ctr Geriatr, Shenzhen Clin Res Ctr Geriatr,Clin Med Coll 2, Guangzhou, Peoples R China
[4] Southern Univ Sci & Technol, Affiliated Hosp 1, Shenzhen 518000, Peoples R China
[5] Shenzhen Peoples Hosp, Biobank Natl Innovat Ctr Adv Med Devices, Shenzhen 518000, Peoples R China
基金
中国国家自然科学基金;
关键词
MESENCHYMAL TRANSITION; RENAL FIBROSIS; EXPRESSION; CELLS; MICRORNAS; CANCER; INHIBITION; MECHANISMS; REPRESSION;
D O I
10.1016/j.isci.2023.108131
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Transforming growth factor beta 1 (TGF beta 1) 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-beta receptor 1, thereby ameliorating renal fibrosis by suppressing the TGF-beta signaling pathway. Furthermore, we found that TGF-beta 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.
引用
收藏
页数:20
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