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- Title
STAT3-induced upregulation of lncRNA TTN-AS1 aggravates podocyte injury in diabetic nephropathy by promoting oxidative stress.
- Authors
Wang, Wenzhe; Li, Yongxia; Zhu, Fan; Huang, Yunfang
- Abstract
Background Diabetic nephropathy (DN) is the most common microvascular complication of diabetes mellitus (DM), being the second cause of end-stage renal disease globally. Podocyte injury is closely associated with DN developmen. Our study aimed to investigate the role of long non-coding RNA (lncRNA) TTN-AS1 in DN-associated podocyte injury. Methods The mouse podocyte cell line (MPC5) and human primary podocytes were stimulated by high glucose (HG; 30 nM glucose) to establish the cellular model of DN. Before HG stimulation, both podocytes were transfected with sh-TTN-AS1#1/2 or pcDNA3.1/STAT3 to evaluate the influence of TTN-AS1 knockdown or STAT3 overexpression on HG-induced podocyte injury. TTN-AS1 and STAT3 expression in both podocytes was examined by RT-qPCR. Cell viability and death were assessed by CCK-8 and LDH release assay. ELISA was adopted for testing IL-6 and TNF-α contents in cell supernatants. The levels of oxidative stress markers (ROS, MDA, SOD, and GSH) in cell supernatants were determined by commercial kits. Western blotting was used for measuring the expression of fibrosis markers (fibronectin and α-SMA and podocyte function markers (podocin and nephrin) in podocytes. Results HG stimulation led to decreased cell viability, increased cell death, fibrosis, inflammation, cell dysfunction and oxidative stress in podocytes. However, knockdown of TTN-AS1 ameliorated HG-induced podocyte injury. Mechanically, the transcription factor STAT3 interacted with TTN-AS1 promoter and upregulated TTN-AS1 expression. STAT3 overexpression offset the protective effect of TTN-AS1 silencing on HG-induced podocyte damage. Conclusion Overall, STAT3-mediated upregulation of lncRNA TTN-AS1 could exacerbate podocyte injury in DN through suppressing inflammation and oxidative stress.
- Subjects
DIABETIC nephropathies; TRANSCRIPTION factors; OXIDATIVE stress; LINCRNA; CHRONIC kidney failure; DIABETES complications; WOUNDS &; injuries
- Publication
Toxicology Research, 2024, Vol 13, Issue 3, p1
- ISSN
2045-452X
- Publication type
Article
- DOI
10.1093/toxres/tfae079