title: Long non-coding RNA ASncmtRNA-2 is upregulated in diabetic kidneys and high glucose-treated mesangial cells.
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.
authors.affiliation: Department of Endocrinology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Arthritis Clinic and Research Center, Peking University People's Hospital, Beijing 100044, P.R. China.
authors.forename: Zhao-Yu
authors.initials: ZY
authors.lastname: Chen
authors.affiliation: Department of Endocrinology, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei 050051, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Endocrinology, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei 050051, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Endocrinology, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei 050051, P.R. China.
authors.forename: Jian-Xia
authors.initials: JX
authors.lastname: Ma
authors.affiliation: Department of Endocrinology, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei 050051, P.R. China.
authors.forename: Yu-Kun
authors.initials: YK
authors.lastname: Li
keywords: NL-nitro-L-arginine methyl ester; antisense mitochondrial noncoding RNA2; diabetic nephropathy; high glucose; oxidative stress