Abstract
BackgroundIt has been reported that long non-coding RNAs (lncRNAs) play vital roles in diabetic nephropathy (DN). Our study aims to research the function of lncRNA KCNQ1OT1 in DN cells and the molecular mechanism.MethodsHuman glomerular mesangial cells (HGMCs) and human renal glomerular endothelial cells (HRGECs) were cultured in high glucose (30 mM) condition as models of DN cells. KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1) and miR-18b-5p levels were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The mRNA and protein levels of Sorbin and SH3 domain-containing protein 2 (SORBS2), Type IV collagen (Col-4), fibronectin (FN), transcriptional regulatory factor-beta 1 (TGF-β1), Twist, NF-κB and STAT3 were measured by qRT-PCR and western blot. Cell viability was detected by cell counting kit-8 (CCK-8) assay for selecting the proper concentration of glucose treatment. Additionally, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and flow cytometry assay were employed to determine cell proliferation and apoptosis, respectively. The targets of KCNQ1OT1 was predicted by online software and confirmed by dual-luciferase reporter assay.ResultsKCNQ1OT1 and SORBS2 were elevated in DN. Both knockdown of KCNQ1OT1 and silencing of SORBS2 restrained proliferation and fibrosis and induced apoptosis in DN cells. Besides, Overexpression of SORBS2 restored the KCNQ1OT1 knockdown-mediate effects on proliferation, apoptosis and fibrosis in DN cells. In addition, miR-18b-5p served as a target of KCNQ1OT1 as well as targeted SORBS2. KCNQ1OT1 knockdown repressed NF-ĸB pathway.ConclusionKCNQ1OT1 regulated DN cells proliferation, apoptosis and fibrosis via KCNQ1OT1/miR-18b-5p/SORBS2 axis and NF-ĸB pathway.
Highlights
It has been reported that long non-coding RNAs play vital roles in diabetic nephropathy (DN)
Highlights: 1. KCNQ1OT1 and Sorbin and SH3 domain-containing protein 2 (SORBS2) were upregulated in DN patients and cells
KCNQ1OT1 and SORBS2 were upregulated in DN Firstly, KCNQ1OT1 level in the serum of DN patients was detected by quantitative real-time polymerase chain reaction (qRT-PCR), and the result showed that the level of KCNQ1OT1 was significantly increased in DN patients compared with that in normal group (Fig. 1a)
Summary
It has been reported that long non-coding RNAs (lncRNAs) play vital roles in diabetic nephropathy (DN). Our study aims to research the function of lncRNA KCNQ1OT1 in DN cells and the molecular mechanism. Diabetic nephropathy (DN), a serious complication of diabetes mellitus, is the most pervasive cause of endstage renal disease worldwide [1]. The causes of DN are extremely complicated, including smoking, poor glycemic control, dyslipidemia, environmental and genetic factors. Renal fibrosis is one of the main pathological features of DN. Inflammation could modulate the transforming growth factor β (TGF-β) activities, which is the vital regulator of fibrosis [2]. TGF-β regulated renal fibrosis in DN by activating various molecules such as collagen and fibronectin (FN) [3]. It is very important to understand the theoretical basis of its pathogenesis and search for available therapeutic strategies
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