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长链非编码 RNA TUG1 通过 AMPK/SIRT1 保护肠道上皮细胞免受高糖高脂诱导的损伤。

lncRNA TUG1 protects intestinal epithelial cells from damage induced by high glucose and high fat via AMPK/SIRT1.

机构信息

Department of General Surgery, First Affiliated Hospital of Jiamusi University, Jiamusi, Heilongjiang 154002, P.R. China.

Department of Infectious Diseases, The Central Hospital of Jiamusi City, Jiamusi, Heilongjiang 154002, P.R. China.

出版信息

Mol Med Rep. 2022 Apr;25(4). doi: 10.3892/mmr.2022.12655. Epub 2022 Feb 25.

Abstract

he incidence of obesity and type 2 diabetes mellitus (T2DM) is increasing year by year and shows a trend towards younger age groups worldwide. It has become a disease that endangers the health of individuals all over the world. Among numerous weight loss surgeries, sleeve gastrectomy (SG) has become one of the most common surgical strategies for the treatment of T2DM. However, SG‑mediated alterations to the molecular mechanism of metabolism require further investigation. Thus, reverse transcription‑quantitative PCR was used to detect the expression levels of long non‑coding (lnc)RNA taurine‑upregulated gene 1 (TUG1), Sirtuin 1 (SIRT1), AMP‑activated protein kinase (AMPK) and uncoupling protein 2 (UCP2) in the serum of T2DM patients, as well as in HIEC‑6 and SW480 cells following treatment with high glucose and high fat (HGHF). Protein expression was detected by western blotting. Cell Counting Kit‑8 assays were performed to analyze cell viability, and flow cytometry and a TUNEL assay was performed to evaluate cell apoptosis. The secretion of ILs in the culture medium was detected by conducting ELISAs. The results showed that lncRNA TUG1 and UCP2 expression was upregulated, SIRT1 and AMPK expression levels were decreased by SG. Under HGHF conditions, HIEC‑6 and SW480 cell viability was inhibited, apoptosis was promoted, TUG1 expression was downregulated, and SIRT1 and AMPK expression levels were upregulated. The secretory levels of IL‑1β, IL‑6 and IL‑8 were increased, whereas the secretion of IL‑10 was decreased under HGHF conditions. lncRNA TUG1 overexpression significantly reversed the effects of HGHF on cell viability, apoptosis and SIRT1, AMPK, UCP2 and Bcl‑2 expression levels. Together, the findings of the present study demonstrated that lncRNA TUG1 alleviated the damage induced by HGHF in intestinal epithelial cells by downregulating SIRT1 and AMPK expression, and upregulating UCP2 expression. Thus, the lncRNA TUG1/AMPK/SIRT1/UCP2 axis may serve an important role in the treatment of T2DM.

摘要

肥胖症和 2 型糖尿病(T2DM)的发病率逐年上升,并呈现出向年轻化发展的趋势。它已成为一种危害全世界个人健康的疾病。在众多减肥手术中,袖状胃切除术(SG)已成为治疗 T2DM 的最常见手术策略之一。然而,SG 介导的代谢分子机制的改变需要进一步研究。因此,采用逆转录-定量 PCR 检测 T2DM 患者及高糖高脂(HGHF)处理的 HIEC-6 和 SW480 细胞血清中长链非编码(lnc)RNA 牛磺酸上调基因 1(TUG1)、Sirtuin 1(SIRT1)、AMP 激活蛋白激酶(AMPK)和解偶联蛋白 2(UCP2)的表达水平。采用蛋白质印迹法检测蛋白表达。通过细胞计数试剂盒-8 分析细胞活力,通过流式细胞术和 TUNEL 分析评估细胞凋亡。通过酶联免疫吸附试验检测培养基中细胞因子的分泌情况。结果显示,SG 使 lncRNA TUG1 和 UCP2 的表达上调,SIRT1 和 AMPK 的表达水平降低。在 HGHF 条件下,HIEC-6 和 SW480 细胞活力受到抑制,凋亡受到促进,TUG1 表达下调,SIRT1 和 AMPK 表达水平上调。IL-1β、IL-6 和 IL-8 的分泌水平升高,而 IL-10 的分泌水平降低。lncRNA TUG1 过表达可显著逆转 HGHF 对细胞活力、凋亡以及 SIRT1、AMPK、UCP2 和 Bcl-2 表达水平的影响。综上所述,本研究结果表明,lncRNA TUG1 通过下调 SIRT1 和 AMPK 表达以及上调 UCP2 表达,减轻 HGHF 对肠上皮细胞的损伤。因此,lncRNA TUG1/AMPK/SIRT1/UCP2 轴可能在治疗 T2DM 中发挥重要作用。

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