Long noncoding RNA Glis2 regulates podocyte mitochondrial dysfunction and apoptosis in diabetic nephropathy via sponging miR‐328‐5p

• Published in: Journal of cellular and molecular medicine Vol. 28; no. 7; pp. e18204 - n/a
• Main Authors: Wang, Ting, Chen, Yanxia, Liu, Zhihong, Zhou, Jing, Li, Na, Shan, Yue, He, Yinxi
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.04.2024; John Wiley and Sons Inc
• Subjects: Animals; Apoptosis; Apoptosis - genetics; Biotechnology; Cell culture; competing endogenous RNA (ceRNA); Creatinine; Diabetes; Diabetes mellitus; Diabetes Mellitus, Experimental - genetics; Diabetes Mellitus, Experimental - pathology; Diabetic Nephropathies - genetics; Diabetic Nephropathies - pathology; Diabetic nephropathy; diabetic nephropathy (DN); Flow cytometry; Glucose; Kidneys; long noncoding RNAs (lncRNAs); Membrane potential; Mice; MicroRNAs - genetics; miRNA; Mitochondria; Mitochondrial Diseases - pathology; mitochondrial dysfunction; Nephropathy; Non-coding RNA; Original; Plasmids; podocyte apoptosis; Podocytes - pathology; RNA, Long Noncoding - genetics; SIRT1 protein; Transcription Factors; Transmission electron microscopy; Ultrastructure; Beijing China; United States > US; China; Japan; long noncoding RNAs (lncRNAs); mitochondrial dysfunction; competing endogenous RNA (ceRNA); diabetic nephropathy (DN); podocyte apoptosis
• ISSN: 1582-1838; 1582-4934; 1582-4934
• DOI: 10.1111/jcmm.18204

Podocyte apoptosis exerts a crucial role in the pathogenesis of DN. Recently, long noncoding RNAs (lncRNAs) have been gradually identified to be functional in a variety of different mechanisms associated with podocyte apoptosis. This study aimed to investigate whether lncRNA Glis2 could regulate podocyte apoptosis in DN and uncover the underlying mechanism. The apoptosis rate was detected by flow cytometry. Mitochondrial membrane potential (ΔΨM) was measured using JC‐1 staining. Mitochondrial morphology was detected by MitoTracker Deep Red staining. Then, the histopathological and ultrastructure changes of renal tissues in diabetic mice were observed using periodic acid‐Schiff (PAS) staining and transmission electron microscopy. We found that lncRNA Glis2 was significantly downregulated in high‐glucose cultured podocytes and renal tissues of db/db mice. LncRNA Glis2 overexpression was found to alleviate podocyte mitochondrial dysfunction and apoptosis. The direct interaction between lncRNA Glis2 and miR‐328‐5p was confirmed by dual luciferase reporter assay. Furthermore, lncRNA Glis2 overexpression alleviated podocyte apoptosis in diabetic mice. Taken together, this study demonstrated that lncRNA Glis2, acting as a competing endogenous RNA (ceRNA) of miRNA‐328‐5p, regulated Sirt1‐mediated mitochondrial dysfunction and podocyte apoptosis in DN.