Wang JunTao, Jiao Peng, Wei XiaoYing, Zhou Yun
Department of Nephrology, The First People's Hospital of Shangqiu, Shangqiu, China.
Department of Emergency, The First People's Hospital of Shangqiu, Shangqiu, China.
Front Physiol. 2021 Nov 11;12:721524. doi: 10.3389/fphys.2021.721524. eCollection 2021.
Acute kidney injury (AKI) is a critical clinical disease characterized by an acute decrease in renal function. Long non-coding RNAs (LncRNAs) are important in AKI. This study aimed to explore the mechanism of lncRNA Kcnq1ot1 in AKI by sponging microRNA (miR)-204-5p as a competitive endogenous RNA (ceRNA). AKI mouse model and hypoxia/reoxygenation (H/R) model of human kidney (HK) cells were established. Kcnq1ot1 expression, cell proliferation, and apoptosis were measured. Binding relations among Kcnq1ot1, miR-204-5p, and NLRP3 were verified. Pathological changes and cell apoptosis were detected. The results showed that Kcnq1ot1 was highly expressed in the AKI model and . Kcnq1ot1 knockdown promoted cell proliferation and prevented apoptosis and inflammation. Furthermore, Kcnq1ot1 inhibited miR-204-5p expression by competitively binding to miR-204-5p in HK-2 cells. miR-204-5p targeted NLRP3 and NLRP3 overexpression averted the inhibiting effect of miR-204-5p on apoptosis and inflammation in HK-2 cells . Kcnq1ot1 knockdown promoted miR-204-5p expression, inhibited NLRP3 inflammasome activation, reduced levels of SCr, BUN, and KIM-1, and thus alleviated AKI and reduced apoptosis. In summary, silencing lncRNA Kcnq1ot1 inhibited AKI by promoting miR-204-5p and inhibiting NLRP3 inflammasome activation.
急性肾损伤（AKI）是一种以肾功能急性下降为特征的严重临床疾病。长链非编码RNA（LncRNAs）在AKI中起重要作用。本研究旨在通过作为竞争性内源RNA（ceRNA）海绵吸附微小RNA（miR）-204-5p来探索lncRNA Kcnq1ot1在AKI中的作用机制。建立了AKI小鼠模型和人肾（HK）细胞的缺氧/复氧（H/R）模型。检测Kcnq1ot1表达、细胞增殖和凋亡情况。验证Kcnq1ot1、miR-204-5p和NLRP3之间的结合关系。检测病理变化和细胞凋亡。结果显示，Kcnq1ot1在AKI模型中高表达。敲低Kcnq1ot1可促进细胞增殖，预防凋亡和炎症。此外，Kcnq1ot1通过在HK-2细胞中与miR-204-5p竞争性结合来抑制miR-204-5p表达。miR-204-5p靶向NLRP3，NLRP3过表达可避免miR-204-5p对HK-2细胞凋亡和炎症的抑制作用。敲低Kcnq1ot1可促进miR-204-5p表达，抑制NLRP3炎性小体激活，降低血清肌酐（SCr）、尿素氮（BUN）和肾损伤分子-1（KIM-1）水平，从而减轻AKI并减少凋亡。综上所述，沉默lncRNA Kcnq1ot1通过促进miR-204-5p和抑制NLRP3炎性小体激活来抑制AKI。
