Chen Li, Xu Jun-Ying, Tan Hong-Bao
Department of Nephrology, Brain Hospital of Hunan Province, Changsha, 410007, Hunan Province, P.R. China.
Department of Anesthesiology, The Fourth Hospital of Changsha, No.70, Lushan Road, Yuelu District, Changsha, 410006, Hunan Province, P.R. China.
J Inflamm (Lond). 2021 Mar 4;18(1):12. doi: 10.1186/s12950-021-00278-4.
Acute kidney injury (AKI) results from renal dysfunction caused by various causes, resulting in high mortality. The underlying mechanisms of ischemia-reperfusion (I/R) induced AKI is very complicated and needed for further research. Here, we sought to found out the functions of lncRNA TUG1 in I/R-induced AKI.
In vivo model was constructed by I/R-induced mice and in vitro model was constructed by hypoxia/reoxygenation (H/R)-induced HK-2 cell. Kidney tissue damage was evaluated through H&E staining in mice. Cell flow cytometry was used to detect the degree of apoptosis. TUG1, miR-494-3p and E-cadherin were determined both by RT-PCR and western blot. Dual luciferase assay was employed to validate the relationships between TUG1, miR-494-3p and E-cadherin. Inflammatory factors including IL-1β, TNFɑ and IL-6 were evaluated by ELISA.
lncRNA TUG1 was decreased while miR-494-3p was elevated in vivo and in vitro. Overexpression of TUG1 or transfection with miR-494-3p inhibitor significantly alleviated cell apoptosis. MiR-494-3p directly targeted E-cadherin and TUG1 suppressed cell apoptosis via serving as a miR-494-3p sponge to disinhibit E-cadherin.
lncRNA TUG1 alleviated I/R-induced AKI through targeting miR-494-3p/E-cadherin.
急性肾损伤（AKI）由多种原因导致的肾功能障碍引起，死亡率很高。缺血再灌注（I/R）诱导的AKI的潜在机制非常复杂，需要进一步研究。在此，我们试图探究长链非编码RNA TUG1在I/R诱导的AKI中的作用。
通过I/R诱导的小鼠构建体内模型，通过缺氧/复氧（H/R）诱导的HK-2细胞构建体外模型。通过苏木精-伊红（H&E）染色评估小鼠肾脏组织损伤。采用细胞流式术检测细胞凋亡程度。通过逆转录-聚合酶链反应（RT-PCR）和蛋白质免疫印迹法检测TUG1、miR-494-3p和E-钙黏蛋白。采用双荧光素酶报告基因检测法验证TUG1、miR-494-3p和E-钙黏蛋白之间的关系。通过酶联免疫吸附测定法（ELISA）评估包括白细胞介素-1β（IL-1β）、肿瘤坏死因子α（TNFɑ）和白细胞介素-6（IL-6）在内的炎症因子。
lncRNA TUG1在体内和体外均降低，而miR-494-3p升高。TUG1过表达或转染miR-494-3p抑制剂可显著减轻细胞凋亡。miR-494-3p直接靶向E-钙黏蛋白，TUG1通过作为miR-494-3p的海绵来解除对E-钙黏蛋白的抑制，从而抑制细胞凋亡。
lncRNA TUG1通过靶向miR-494-3p/E-钙黏蛋白减轻I/R诱导的AKI。
