Department of Thoracic Surgery, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining city, Shandong Province, P.R.China.
Department of Endocrinology, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining city, Shandong Province, P.R.China.
PLoS One. 2021 Jun 7;16(6):e0252761. doi: 10.1371/journal.pone.0252761. eCollection 2021.
Long non-coding RNAs (lncRNAs) are important regulators in diabetic nephropathy. In this study, we investigated the potential role of lncRNA TUG1 in regulating endoplasmic reticulum stress (ERS)-mediated apoptosis in high glucose induced renal tubular epithelial cells. Human renal tubular epithelial cell line HK-2 was challenged with high glucose following transfection with lncRNA TUG1, miR-29c-3p mimics or inhibitor expression plasmid, either alone or in combination, for different experimental purposes. Potential binding effects between TUG1 and miR-29c-3p, as well as between miR-29c-3p and SIRT1 were verified. High glucose induced apoptosis and ERS in HK-2 cells, and significantly decreased TUG1 expression. Overexpressed TUG1 could prevent high glucose-induced apoptosis and alleviated ERS via negatively regulating miR-29c-3p. In contrast, miR-29c-3p increased HK-2 cells apoptosis and ERS upon high glucose-challenge. SIRT1 was a direct target gene of miR-29c-3p in HK-2 cells, which participated in the effects of miR-29c-3p on HK-2 cells. Mechanistically, TUG1 suppressed the expression of miR-29c-3p, thus counteracting its function in downregulating the level of SIRT1. TUG1 regulates miR-29c-3p/SIRT1 and subsequent ERS to relieve high glucose induced renal epithelial cells injury, and suggests a potential role for TUG1 as a promising diagnostic marker of diabetic nephropathy.
长链非编码 RNA(lncRNA)是糖尿病肾病的重要调控因子。在本研究中,我们研究了 lncRNA TUG1 在调节高糖诱导的肾小管上皮细胞内质网应激(ERS)介导的细胞凋亡中的潜在作用。人肾小管上皮细胞系 HK-2 在转染 lncRNA TUG1、miR-29c-3p 模拟物或抑制剂表达质粒后,单独或组合进行不同实验目的的高糖刺激。验证了 TUG1 与 miR-29c-3p 之间,以及 miR-29c-3p 与 SIRT1 之间的潜在结合效应。高糖诱导 HK-2 细胞凋亡和 ERS,并显著降低 TUG1 表达。过表达 TUG1 可通过负调控 miR-29c-3p 预防高糖诱导的细胞凋亡和减轻 ERS。相反,miR-29c-3p 在高糖刺激下增加 HK-2 细胞的凋亡和 ERS。SIRT1 是 HK-2 细胞中 miR-29c-3p 的直接靶基因,参与了 miR-29c-3p 对 HK-2 细胞的作用。机制上,TUG1 抑制了 miR-29c-3p 的表达,从而抵消了其下调 SIRT1 水平的功能。TUG1 通过调节 miR-29c-3p/SIRT1 及其随后的 ERS 来缓解高糖诱导的肾小管上皮细胞损伤,提示 TUG1 作为糖尿病肾病有希望的诊断标志物的潜在作用。