miR-34b-3p protects against acute kidney injury in sepsis mice via targeting ubiquitin-like protein 4A

MicroRNAs (miRNAs) have been reported as a diagnostic markers for sepsis, and miRNAs have also been found to play a regulatory role in sepsis-induced acute kidney injury (AKI). However, the regulatory effect and mechanism of miR-34b-3p on AKI remains elusive. First, sepsis mice with AKI was established via cecal ligation puncture (CLP), and verified through hematoxylin-eosin staining, determination of tumor necrosis factor-ix (TNF-alpha), interleukin (IL)-6/1 beta and serum levels of alanine aminotransferase (ALT) and blood urea nitrogen (BUN). Data showed that CLP-induced mice demonstrated increased ALT, BUN, TNE-alpha, IL-1 beta, and IL-6 with injured pathological morphology of kidney tissues. Second, lipopolysaccharide (LPS) treatment elevated TNE-alpha, IL-1 beta, and IL-6 contents in rat mesangial cells (RMCs). MiR-34b-3p was down regulated in both CLP-induced mice and LPS-induced RMCs. Third, target gene of miR-34b-3p was verified as ubiquitin-like protein 4A (UBL4A), and UBL4A was unregulated in LPS-induced RMCs. MiR-34b-3p could inhibit UBL4A expression and decreased TNE-alpha, IL-1 beta and IL-6 contents in LPS-induced RMCs, while overexpression of UBL4A counteract with the suppressive effects of miR-34b-3p on the protein expression. Moreover, transcriptional activity of UBL4A-induced NE-KB was decreased by miR-34b-3p. Lastly, in vivo injection of miR-34b-3p agomir improved CLP-induced kidney tissues injury with declined ALT, BUN, TNE-alpha, IL-1 beta, IL-6, and UBL4A. In general, miR-34b-3p overexpression could alleviate AKI in sepsis mice through downregulation of UBL4A/NF-kappa B, providing potential therapeutic strategy for AKI.