Effects and Mechanism of lncRNA CRNDE on Sepsis-Induced Acute Kidney Injury
Shen Wu, Hengyi Qiu, Qiao Wang, Zheng Cao, Jianmin Wang
Abstract
Objective . To investigate the effects of lncRNA CRNDE on sepsis-associated acute kidney injury in the human kidney 2 cell line and explore the potential mechanisms. Methods . HK-2 cells were treated with lipopolysaccharides to induce injuries. The expression of CRNDE and miR-146a in HK-2 cells were altered by a transient transfection assay. Cell apoptosis was detected by a flow cytometry assay, and the levels of inflammatory cytokines including TNF- α , IL-6, IL-8, and IL-1 β were assessed by ELISA. Furthermore, western blot analysis was performed to detect the expression levels of TLR4/NF- κ B pathway-related proteins. And a luciferase reporter gene assay was used to verify if miR-146a was the target of CRNDE. Results . LPS treatment increased CRNDE expression in HK-2 cells. CRNDE overexpression enhanced cell injuries in HK-2 cells significantly increasing inflammatory cytokine levels, including TNF- α , IL-6, IL-8, and IL-1 β , and cell apoptosis. In addition, CRNDE overexpression further activated the TLR4/NF- κ B pathways in HK-2 cells. Inversely, opposite results were observed in the miR-146a mimic treatment group, and the miR-146a inhibitor could reverse the protein expression changes of TLR4/NF- κ B in the si-CRNDE and LPS treatment group. Conclusion . This study demonstrated that CRNDE overexpression could activate the TLR4/NF- κ B signaling pathway by regulating miR-146a, which accelerated LPS-induced inflammation and apoptosis in HK-2 cells.