MicroRNA‑93 inhibits the apoptosis and inflammatory response of tubular epithelial cells via the PTEN/AKT/mTOR pathway in acute kidney injury

Abstract

Renal tubular epithelial cell injury is the main cause of septic acute kidney injury (AKI), which is characterized by the excessive inflammatory response and apoptosis. Numerous studies have demonstrated that miRNAs are associated with inflammatory response and apoptosis in numerous diseases. The present study mainly focuses on investigating the association between microRNA (miRNA/miR) expression and inflammatory response and apoptosis in the pathogenesis of AKI. <em>In vitro</em> and <em>in vivo</em> models of AKI were simulated using <em>Escherichia coli</em> lipopolysaccharide (LPS)‑administrated kidney epithelial cells and mice, respectively. The miRNA expression profile was examined using miRNA microarray in kidney tissues. Next, the effects of miR‑93 upregulation on the apoptosis, cytokine expression and oxidative stress in the LPS‑stimulated TCMK‑1 were tested. The target genes of this miRNA were investigated, and the regulatory association between miR‑93 and the AKT/mTOR pathway was investigated. The results demonstrated that miR‑93 was the most downregulated miRNA in mice kidney. Furthermore, in LPS‑induced renal tubular epithelial cells (TECs) injury model, that upregulation of miR‑93 was found to attenuate the apoptosis and inflammatory response, as well as reactive oxygen species generation. Mechanistically, phosphatase and tensin homolog deleted on chromosome 10 (PTEN) was identified as a target of miR‑93. Further experiments revealed that LPS‑induced the decrease of phosphorylated (p)‑AKT and p‑mTOR protein expression<em> in vitro</em> are reversed by the overexpression of miR‑93. The results of the present study suggested that the protective effect of miR‑93 on AKI may be associated with the activation of PTEN/AKT/mTOR pathway. miR‑93 may serve as a potential therapeutic target in sepsis‑induced AKI.

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