Yang Jing, Li Lihua, Hong Shijun, Zhou Zhu, Fan Wenxing
Department of Nephrology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, P.R. China.
Department of Forensic Toxicology, Kunming Medical University, Kunming, Yunnan 650500, P.R. China.
Exp Ther Med. 2019 Jul;18(1):119-124. doi: 10.3892/etm.2019.7542. Epub 2019 May 3.
Previous studies have revealed that long intergenic non-coding RNA for kinase activation (LINK-A), a long non-coding RNA (lncRNA) promotes disease progression in triple-negative breast cancer by activating hypoxia-inducible factor 1α (HIF1α). However, the activation of HIF1α has also been demonstrated to improve diabetic nephropathy. It is therefore reasonable to expect that LINK-A may also participate in diabetic nephropathy. In the current study, the expression of LINK-A lncRNA and HIF1α was determined in renal biopsies of patients with diabetic nephropathy. LINK-A lncRNA and HIF1α expression levels were detected by reverse transcription quantitative (RT-q) PCR and ELISA in diabetic patients without complications and used as controls. Correlations between LINK-A lncRNA and HIF1α expression were analyzed using Pearson's correlation coefficient. Effects of lncRNA and HIF1α overexpression on LINK-A lncRNA expression, HIF1α expression and cell apoptosis were assessed using RT-qPCR, western blotting and a cell apoptosis assay. The results revealed that LINK-A lncRNA and HIF1α were downregulated in patients with diabetic nephropathy, as well as in diabetic patients without complications. The lowest expression of LINK-A lncRNA and HIF1α were observed in healthy controls. A positive correlation was identified between LINK-A lncRNA and HIF1α in both patients groups, but not in the control group. LINK-A lncRNA and HIF1α overexpression inhibited the apoptosis of mouse podocyte cells under a high glucose treatment. LINK-A lncRNA overexpression also promoted HIF1α expression in mouse podocyte cells, while HIF1α overexpression did not significantly affect LINK-A lncRNA expression. In conclusion, LINK-A lncRNA may activate HIF1α signaling resulting in the improvement of diabetic nephropathy treatment.
先前的研究表明，激酶激活长链基因间非编码RNA（LINK-A），一种长链非编码RNA（lncRNA），通过激活缺氧诱导因子1α（HIF1α）促进三阴性乳腺癌的疾病进展。然而，HIF1α的激活也已被证明可改善糖尿病肾病。因此，可以合理推测LINK-A也可能参与糖尿病肾病。在本研究中，测定了糖尿病肾病患者肾活检组织中LINK-A lncRNA和HIF1α的表达。通过逆转录定量（RT-q）PCR和ELISA检测无并发症糖尿病患者的LINK-A lncRNA和HIF1α表达水平，并将其作为对照。使用Pearson相关系数分析LINK-A lncRNA与HIF1α表达之间的相关性。使用RT-qPCR、蛋白质免疫印迹法和细胞凋亡检测评估lncRNA和HIF1α过表达对LINK-A lncRNA表达、HIF1α表达和细胞凋亡的影响。结果显示，糖尿病肾病患者以及无并发症糖尿病患者中LINK-A lncRNA和HIF1α均下调。在健康对照中观察到LINK-A lncRNA和HIF1α的表达最低。在两个患者组中均发现LINK-A lncRNA与HIF1α呈正相关，但在对照组中未发现。在高糖处理下，LINK-A lncRNA和HIF1α过表达抑制了小鼠足细胞的凋亡。LINK-A lncRNA过表达还促进了小鼠足细胞中HIF1α的表达，而HIF1α过表达对LINK-A lncRNA表达没有显著影响。总之，LINK-A lncRNA可能激活HIF1α信号通路，从而改善糖尿病肾病的治疗。
