LncRNA MALAT1-deficiency restrains lipopolysaccharide (LPS)-induced pyroptotic cell death and inflammation in HK-2 cells by releasing microRNA-135b-5p.

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.