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

iScience (Nov 2023)

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

Affiliations

Shu Yang: 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.
Kewei Jiang: 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.
Lixing Li: 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.
Jiaqing Xiang: 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.
Yanchun Li: 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.
Lin Kang: 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.; The Biobank of National Innovation Center for Advanced Medical Devices, Shenzhen People’s Hospital, Shenzhen 518000, China; Corresponding author
Guangyan Yang: 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.; Corresponding author
Zhen Liang: 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.; Corresponding author

Journal volume & issue: Vol. 26, no. 11
p. 108131

Abstract

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Summary: 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.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

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