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

Shu Yang; Kewei Jiang; Lixing Li; Jiaqing Xiang; Yanchun Li; Lin Kang; Guangyan Yang; Zhen Liang

doi:10.1016/j.isci.2023.108131

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

iScience. 2023 Oct 5;26(11):108131. doi: 10.1016/j.isci.2023.108131. eCollection 2023 Nov 17.

Authors

Shu Yang^{1

2}, Kewei Jiang^{1

2}, Lixing Li^{1

2}, Jiaqing Xiang^{1

2}, Yanchun Li^{1

2}, Lin Kang^{1

2

3}, Guangyan Yang^{1

2}, Zhen Liang^{1

2}

Affiliations

¹ 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.
² 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.
³ The Biobank of National Innovation Center for Advanced Medical Devices, Shenzhen People's Hospital, Shenzhen 518000, China.

Abstract

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.

Keywords: Biological sciences; Cell biology; Fibrosis; Molecular biology.