LncRNA PVT1 Regulates High Glucose-Induced Viability, Oxidative Stress, Fibrosis, and Inflammation in Diabetic Nephropathy via miR-325-3p/Snail1 Axis

• Main Authors: Qin B, Cao X
• Format: Article
• Language: English
• Published: Dove Medical Press 2021-04-01
• Series: Diabetes, Metabolic Syndrome and Obesity : Targets and Therapy
• Subjects: diabetic nephropathy; lncrna pvt1; mir-325-3p; snail1
• Online Access: https://www.dovepress.com/lncrna-pvt1-regulates-high-glucose-induced-viability-oxidative-stress--peer-reviewed-fulltext-article-DMSO

Baoyu Qin,1 Xiaoli Cao2 1Division of Endocrinology and Metabolic, Department of Geriatrics, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Zhuang Autonomous Region, People’s Republic of China; 2Department of Endocrinology, Shanxi Cardiovascular Hospital, Taiyuan, 030024, Shanxi Province, People’s Republic of ChinaCorrespondence: Baoyu QinDivision of Endocrinology and Metabolic, Department of Geriatrics, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning, 530021, Guangxi Zhuang Autonomous Region, People’s Republic of ChinaTel [phone]Email [e-mail]: Diabetic nephropathy (DN), as a complication of diabetes, is a leading cause of mortality in diabetic patients. It has been reported that lncRNA PVT1 (PVT1) could accelerate the progression of DN by promoting ECM accumulation and increasing the expression of fibronectin 1 (FN1). However, the underlying mechanism of PVT1 on DN remains unknown.Methods: To study the effect of PVT1 on DN, mice were injected 50 mg/kg STZ to build the DN models. Mesangial cells (MCs) were induced by high glucose as in vitro model of DN. The expression level of PVT1, miR-325-3 and Snail1 was assessed by qRT-PCR and Western blot. Luciferase reporter assay, RNA pull-down and RIP were used to explore the interaction among PVT1, miR-325-3 and Snail1.Results: In in vivo and in vitro DN models, the expression of PVT1 was upregulated. High glucose (HG) induced cell viability, oxidative stress, fibrosis and inflammation in MCs, which were reversed in the PVT1-KD MCs. The level of miR-325-3p was also increased in in vivo and in vitro experiments. Additionally, PVT1 can directly bind to miR-325-3p. Finally, Snail1 was a direct target of miR-325-3p.Conclusion: PVT1 inhibits viability, oxidative stress, fibrosis, and inflammation in DN via miR-325-3p/Snail1 axis.Keywords: diabetic nephropathy, lncRNA PVT1, miR-325-3p, Snail1