Wuhan Fourth Hospital, Puai Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, PR China.
Ren Fail. 2021 Dec;43(1):1288-1297. doi: 10.1080/0886022X.2021.1974037.
Long non-coding RNAs (LncRNAs) participate in the regulation of chronic kidney disease (CKD), and acute kidney injury (AKI) is identified as an important risk factor for CKD. This study investigated the involvement of a novel LncRNA MALAT1 in regulating lipopolysaccharide (LPS)-induced cell pyroptosis and inflammation in the human renal tubular epithelial HK-2 cells. Here, the HK-2 cells were subjected to LPS (2 μg/mL) treatment to establish cellular AKI models , and we validated that LPS triggered NLRP3-mediated pyroptotic cell death, promoted cell apoptosis and inflammation-associated cytokines secretion to induce HK-2 cell injury. Then, a novel LncRNA MALAT1/miRNA (miRNA)-135b-5p axis was verified to rescue cell viability in LPS treated HK-2 cells by targeting NLRP3. Mechanistically, miRNA-135b-5p bound to LncRNA MALAT1, and LncRNA MALAT1 positively regulated NLRP3 through acting as RNA sponger for miRNA-135b-5p. Further gain- and loss-of-function experiments evidenced that both LncRNA MALAT1 ablation and miRNA-135b-5p overexpression reversed LPS-induced cell pyroptosis, apoptosis, and inflammation in the HK-2 cells, and the protective effects of LncRNA MALAT1 knock-down on LPS-treated HK-2 cells were abrogated by silencing miRNA-135b-5p. In general, our study firstly investigated the role of the LncRNA MALAT1/ miRNA-135b-5p/NLRP3 signaling cascade in regulating LPS-induced inflammatory death in HK-2 cells.
长链非编码 RNA（lncRNAs）参与慢性肾脏病（CKD）的调节，急性肾损伤（AKI）被认为是 CKD 的重要危险因素。本研究探讨了新型 lncRNA MALAT1 在调节脂多糖（LPS）诱导的人肾小管上皮 HK-2 细胞细胞焦亡和炎症中的作用。在此，用 LPS（2μg/ml）处理 HK-2 细胞建立细胞 AKI 模型，验证 LPS 触发 NLRP3 介导的细胞焦亡性细胞死亡，促进细胞凋亡和炎症相关细胞因子分泌，导致 HK-2 细胞损伤。然后，验证了一种新型 lncRNA MALAT1/miRNA（miRNA）-135b-5p 轴通过靶向 NLRP3 来挽救 LPS 处理的 HK-2 细胞中的细胞活力。机制上，miRNA-135b-5p 与 lncRNA MALAT1 结合，lncRNA MALAT1 通过作为 miRNA-135b-5p 的 RNA 海绵正向调节 NLRP3。进一步的增益和缺失功能实验表明，lncRNA MALAT1 敲除和 miRNA-135b-5p 过表达均逆转了 LPS 诱导的 HK-2 细胞细胞焦亡、凋亡和炎症，沉默 miRNA-135b-5p 消除了 lncRNA MALAT1 敲低对 LPS 处理的 HK-2 细胞的保护作用。总之，本研究首次研究了 lncRNA MALAT1/miRNA-135b-5p/NLRP3 信号通路在调节 LPS 诱导的 HK-2 细胞炎症性死亡中的作用。
