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-α (TNF-α), interleukin (IL)-6/1ß and serum levels of alanine aminotransferase (ALT) and blood urea nitrogen (BUN). Data showed that CLP-induced mice demonstrated increased ALT, BUN, TNF-α, IL-1ß, and IL-6 with injured pathological morphology of kidney tissues. Second, lipopolysaccharide (LPS) treatment elevated TNF-α, IL-1ß, and IL-6 contents in rat mesangial cells (RMCs). MiR-34b-3p was downregulated 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 upregulated in LPS-induced RMCs. MiR-34b-3p could inhibit UBL4A expression and decreased TNF-α, IL-1ß 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 NF-κB 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, TNF-α, IL-1ß, IL-6, and UBL4A. In general, miR-34b-3p overexpression could alleviate AKI in sepsis mice through downregulation of UBL4A/NF-κB, providing potential therapeutic strategy for AKI.

LncRNA PEAMIR inhibits apoptosis and inflammatory response in PM2.5 exposure aggravated myocardial ischemia/reperfusion injury as a competing endogenous RNA of miR-29b-3p.

The sensitivity of myocardium is enhanced to ischemia/reperfusion (I/R) injury under PM2.5 exposure. It is still under prelude for lncRNA-miRNA pair in the study of aggravated myocardial I/R injury under PM2.5 exposure. In this study, we first built a rat model of 30 min ischemia and 24 h reperfusion followed PM2.5 (6.0 mg/kg) exposure. We found PM2.5 exposure could obviously aggravate I/R injury in the fields of myocardium damage, apoptosis levels and cardiac function which were evaluated by TTC staining, TUNEL and echocardiography, respectively. Then, based on results of sequencing and RT-qPCR, we selected NONRATT003473.2 in the follow-up experiments and named this lncRNA as PM2.5 exposure aggravated myocardial I/R injury lncRNA (PEAMIR). Consistent with the results rat model, we confirmed PEAMIR to be a protective lncRNA against PM + HR triggered damages in H9c2 cells. Next, according to the bioinformatics analysis from miRanda database and a series of gain- and loss-of-function experiments, we proved PEAMIR to be a ceRNA for miR-29b-3p to inhibit cardiac inflammation and apoptosis. Finally, using Target-Scan database, the conserved binding sites for miR-29b-3p was identified in the 3'UTR of PI3K (p85a), a key protein of apoptosis. Our subsequent experiments validated the regulatory relationship between PEAMIR-miR-29b-3p ceRNA pair and PI3K (p85a)/Akt/GSK3b/p53 cascade pathway. In conclusion, our study demonstrated the role and mechanism of PEAMIR in the augment of I/R injury under PM2.5 exposure, suggesting a promising strategy for the prevention and treatment of I/R injury under PM2.5 exposure.