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Iranian Journal of Kidney Diseases، جلد ۱۸، شماره ۰۳، صفحات ۱۶۸-۱۷۸

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عنوان انگلیسی MiR-33a Overexpression Exacerbates Diabetic Nephropathy Through Sirt6-dependent Notch Signaling
چکیده انگلیسی مقاله 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 upregulated 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
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نویسندگان مقاله | Yingying Wang
Department of Pediatrics, Nanyang Second General Hospital, Nanyang 473000, Henan, PR China


| Shasha Dai
Department of Infection, Children’s Hospital of Nanjing Medical University, Nanjing 210000, Jiangsu, PR China


| Jing Yang
Department of Infection, Children’s Hospital of Nanjing Medical University, Nanjing 210000, Jiangsu, PR China


| Jun Ma
Department of Pediatrics, Nanyang Second General Hospital, Nanyang 473000, Henan, PR China


| Peng Wang
Department of Pediatrics, Nanyang Second General Hospital, Nanyang 473000, Henan, PR China


| Xiaowei Zhao
Department of Pediatrics, Nanyang Second General Hospital, Nanyang 473000, Henan, PR China


| Jua Liu
Department of Pediatrics, Nanyang Second General Hospital, Nanyang 473000, Henan, PR China


| Ao Xiao
Department of Pediatrics, Nanyang Second General Hospital, Nanyang 473000, Henan, PR China


| Yahui Song
Department of Pediatrics, Nanyang Second General Hospital, Nanyang 473000, Henan, PR China


| Lipin Gao
Department of Pediatrics, Nanyang Second General Hospital, Nanyang 473000, Henan, PR China



نشانی اینترنتی https://ijkd.org/index.php/ijkd/article/view/7904
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کد مقاله (doi) 10.52547/g7kbp983
زبان مقاله منتشر شده en
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نوع مقاله منتشر شده ORIGINAL | Kidney Diseases
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