Inhibition of the LncRNA Prevents Podocyte Injury and Mitotic Catastrophe in Diabetic Nephropathy

Overview

Journal Mol Ther Nucleic Acids

Publisher Cell Press

Date 2022 Apr 11

PMID 35402074

Authors

Ziyang Wang

Ying Chang

Yue Liu

Bing Liu

Junhui Zhen

Xiaobing Li

Jiangong Lin

Qun Yu

Zhimei Lv

Rong Wang

Affiliations

Soon will be listed here.

Abstract

Podocyte damage is strongly associated with the progression of diabetic nephropathy. Mitotic catastrophe plays an essential role in accelerating podocyte loss and detachment from the glomerular basement membrane. In the current study, we observed that the long non-coding RNA (lncRNA) was noticeably upregulated in the plasma and kidney tissues of patients with diabetic nephropathy, and this upregulation was accompanied by higher albumin/creatinine ratios and serum creatinine levels. By generating CRISPR-Cas9 -knockout (KO) mice and employing vectors , we found that the depletion of expression significantly restored slit-diaphragm integrity, attenuated foot process effacement, prevented dedifferentiation, and suppressed mitotic catastrophe in podocytes during hyperglycemia. The mechanistic investigation revealed that increased Sox4 expression and subsequently regulated p53 ubiquitination and acetylation, thereby inhibiting the downstream factors CyclinB/cdc2 by enhancing p21 activity, and that interacted with Sox4 by sponging . Additionally, the inhibition of with an antagomir effectively enhanced glomerular podocyte injury and mitotic dysfunction, eventually exacerbating proteinuria. Based on these findings, may represent a therapeutic target for diabetic nephropathy.

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