Long Non-coding RNA MIR22HG Alleviates Ischemic Acute Kidney Injury by Targeting the miR-134-5p/NFAT5 axis.

Abstract

Acute kidney injury (AKI), often triggered by ischemia-reperfusion (I/R) injury, is a critical condition characterized by rapid loss of renal function, leading to high morbidity and mortality. Despite extensive research, therapeutic options for ischemic AKI remain limited, and understanding the molecular mechanisms involved is crucial for developing targeted therapies. Long non-coding RNAs (lncRNAs) have emerged as pivotal regulators of gene expression and cellular processes in various diseases, including cancer and renal injury. This study investigates the role of the lncRNA MIR22HG in mitigating renal injury during ischemic AKI. Using in vivo and in vitro models of I/R-induced AKI in mice and hypoxia/reoxygenation (H/R)-treated renal cells, we demonstrated that MIR22HG expression is significantly downregulated in ischemic AKI conditions. Functional assays showed that overexpression of MIR22HG in these models led to reduced renal cell apoptosis, inflammation, and improved renal function. Mechanistically, MIR22HG exerted its protective effects by negatively regulating miR-134-5p, which in turn alleviated renal injury by upregulating NFAT5, a transcription factor known to mitigate cellular stress. Furthermore, dual-luciferase and RNA pull-down assays confirmed direct interactions between MIR22HG and miR-134-5p, as well as miR-134-5p and NFAT5. Additionally, loss-and-gain-of-function assays demonstrated that overexpression of MIR22HG led to the upregulation of NFAT5, which mitigated renal apoptosis, and inflammation and improved renal function. Collectively, the results of our study highlight the therapeutic potential of targeting the MIR22HG/miR-134-5p/NFAT5 axis in the treatment of ischemic AKI, providing new insights into the molecular regulation of renal cell survival and repair during injury.