Yingying Wang, Shasha Dai, Jing Yang, Jun Ma, Peng Wang, Xiaowei Zhao, Jua Liu, Ao Xiao, Yahui Song, Lipin Gao
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引用次数: 0
Abstract
Introduction: Diabetic nephropathy (DN) belongs to the major cause of end-stage kidney disease. We probed the functions of a microRNA miR-33a in inducing podocytes injury during childhood DN (CDN).
Methods: Kidney samples were collected from 20 children with DN. Matrix deposition and glomerular basement membranes thickness were examined by periodic acid-Schiff staining. Immunofluorescence staining was performed to assess kidney function-related proteins. MicroRNA (MiR)-33a mimic together with miR-33a inhibitor was transfected into podocytes for determining the roles of miR-33a. Glomerular podocyte apoptosis was determined by terminal deoxynucleotidyl transferase (TdT) dUTP Nick-End Labeling (TUNEL) staining along with flow cytometry.
Results: Down-regulation of Nephrin and Podocin and increased podocyte apoptosis rate were observed in the glomerulus of CDN as well as podocytes treated with high glucose. MiR-33a was up regulated in the glomeruli and glucose-treated podocytes. Injury in podocytes was aggravated with miR-33a elevation but alleviated with miR-33a inhibition. Moreover, the expression of Sirtuin 6 (Sirt6) was decreased while the levels of notch receptor 1 (Notch1) and notch receptor 4 (Notch4) were elevated in the glomerulus and glucose-treated podocytes. Decreased level of Sirt6 upon glucose treatment was abrogated by miR-33a inhibition, and the podocytes injury induced by glucose exposure was relieved by Sirt6 via Notch signaling.
Conclusion: These findings indicated that miR-33a promoted podocyte injury via targeting Sirt6-dependent Notch signaling in CDN, which might provide a novel sight for CDN treatment. DOI: 10.52547/ijkd.7904.
期刊介绍：
The Iranian Journal of Kidney Diseases (IJKD), a peer-reviewed journal in English, is the official publication of the Iranian Society of Nephrology. The aim of the IJKD is the worldwide reflection of the knowledge produced by the scientists and clinicians in nephrology. Published quarterly, the IJKD provides a new platform for advancement of the field. The journal’s objective is to serve as a focal point for debates and exchange of knowledge and experience among researchers in a global context. Original papers, case reports, and invited reviews on all aspects of the kidney diseases, hypertension, dialysis, and transplantation will be covered by the IJKD. Research on the basic science, clinical practice, and socio-economics of renal health are all welcomed by the editors of the journal.
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