Long non-coding RNA ASncmtRNA-2 is upregulated in diabetic kidneys and high glucose-treated mesangial cells

Abstract

Abstract. Diabetic nephropathy (DN) is one of the most frequent complications associated with type I and II diabetes mellitus. Kidneys from patients with DN are characterized by mesangial matrix expansion and increased thickness of the glomerular basement membrane, which are induced by reactive oxygen species (ROS) production. Previous studies have been conducted to investigate this; however, the detailed mechanism of DN progression remains to be elucidated. The present study evaluated the expression of antisense mitochondrial non-coding RNA-2 (ASncmtRNA-2) in an experimental DN model and cultured human mesangial cells. When mice that exhibited genetic type II diabetes developed DN, ASncmtRNA-2 expression was significantly increased (P=0.017) and was positively correlated with pro-fibrotic factor transforming growth factor β1 (TGFβ1) expression and its downstream gene, fibronectin. Inhibition of ROS through administration of the nitric oxide synthase inhibitor, NG-nitro-L-Arginine methylester (L-NAME), significantly reduced (P=0.022) the upregulation of ASncmtRNA-2 in DN. In cultured human renal mesangial cells (HRMCs), ASncmtRNA-2 was upregulated by high glucose stimuli in a time-dependent manner. Glucose-induced upregulation of ASncmtRNA-2 was also reduced by co-incubation of HRMCs with L-NAME. Notably, specific short hairpin RNA against ASncmtRNA-2 significantly downregulated the expression of TGFβ1 in HRMCs. The present study suggests that ASncmtRNA-2 is upregulated by ROS and may promote glomerular fibrosis in DN via positively regulating the expression of pro-fibrotic factors. These findings may provide novel potential therapeutic and preventative treatments for DN.

Silencing of LncRNA PVT1 inhibits the proliferation, migration and fibrosis of high glucose-induced mouse mesangial cells via targeting microRNA-93-5p

“…lncRNAs play important regulatory roles in the progression of DN. Gao et al proved that lncRNA-ASncmtRNA-2 is up-regulated in DN kidney tissues and HG-treated MCs, and its overexpression promotes the glomerular fibrosis in DN [29]. Li et al showed that lncRNA-1700020I14Rik contributes to the fibrosis of MMCs cultured with HG medium [30].…”

The Big Entity of New RNA World: Long Non-Coding RNAs in Microvascular Complications of Diabetes

“…Furthermore, ASncmtRNA-2 upregulation was accompanied by increase in TGFβ1 and its downstream gene, fibronectin . These authors have proposed that ROS mediated upregulation of ASncmtRNA-2 promotes DN through increased transcription of pro-fibrotic factors ( 33 ).…”

Mitoepigenetics and Its Emerging Roles in Cancer

“…It expresses in normal proliferating cells. Villegas et al, 2007;Burzio et al, 2009;Rivas et al, 2012;Villota et al, 2012;Vidaurre et al, 2014;Bianchessi et al, 2015;Gao Y. et al, 2017 SncmtRNA-2 (GenBank:…”

“…These two microRNAs target p16 and induce a cell cycle arrest at G2M phase, thereby affecting replicative senescence establishment (Bianchessi et al, 2015). Besides, ASncmtRNA-2 is also upregulated in diabetic kidneys and high glucosetreated mesangial cells and can promote glomerular fibrosis via modulating the expression of pro-fibrotic factors in diabetic nephropathy (Gao Y. et al, 2017).…”