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

Abstract

Background: 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.

lncRNA MSC-AS1 Aggravates Diabetic Nephropathy by Regulating the miR-325/CCNG1 Axis

“…Recently, more and more studies have shown that long noncoding RNA (lncRNA) is involved in the pathogenesis of human diseases including DN. Qin et al reported that lncRNA PVT1 regulated HG-induced viability, oxidative stress, fibrosis, and inflammation in DN through the miR-325-3p/Snail1 axis [ 5 ]. It has been found that knockdown of lncRNA NORAD inhibits the proliferation, inflammation, and fibrosis of human mesangial cells under HG conditions by regulating the miR-485/NRF1 axis [ 6 ].…”

“…Here, miR-325 is predicted to be the downstream target of lncRNA MSC-AS1. MiR-325 has been found to regulate HG-induced viability, oxidative stress, fibrosis, and inflammation in DN through the mediation of lncRNA PVT1 [ 5 ]. In addition, lncRNA MSC-AS1 promoted the progression of colorectal cancer by regulating the miR-325/TRIM14 axis [ 10 ].…”

Plasmacytoma Variant Translocation 1 (PVT1) Gene as a Potential Novel Target for the Treatment of Diabetic Nephropathy

“…The histological collagen deposition should be evaluated in addition to mesangial and glomerular areas [ 43 ]. Lastly, PVT1 may exert its effects on DN progression through other mechanisms besides ECM accumulation, such as podocyte apoptosis [ 16 ], inflammation and oxidative stress [ 44 ], and haemodynamic factors [ 45 ]. Further investigations are needed to delineate the complex network of PVT1 and its interactions with other biological molecules.…”

Diabetes exacerbated sepsis-induced intestinal injury by promoting M1 Macrophage Polarization via miR-3061/Snail1 signaling

“…Snail1 silence has also been revealed to decrease the polarization of M1 macrophages and alleviate the levels of in ammatory cytokines in the study on renal brosis [23]. Within diabetic conditions snail1 expression seems to be particularly upregulated and promotes oxidative stress and in ammation [24]. And snail1 silencing could effectively prevented diabetes-related complications progression [25].…”

“…Snail1, the core transcription factor acting as epithelial to mesenchymal transition (EMT) inducer, has been increasingly considered as a major regulator of macrophage activation. The action of Snail1 has been involved in multiple cellular progresses including tumor invasion and migration, brosis and in ammation [19][20][21]. Whether snail1 in uence the in ammation microenvironment and macrophage polarization has been addressed in those related studies.…”