Background
It has been found that miR-505-5p is closely related to cardiovascular metabolic risk factors. Nonetheless, there is little research analyzing miR-505-5p for its role as well as molecular mechanism in myocardial injury caused by ischemia-reperfusion (I/R).
Conclusion
miR-505-5p can improve I/R-mediated myocardial apoptosis and inflammation by targeting sUmod. In this study, miR-505-5p is related to MIRI pathogenesis, which provides the new possible targeted therapy in patients with MIRI.
Methods
This work utilized quantitative reverse transcriptase PCR (qRT-PCR) for detecting miR-505-5p and serum uromodulin (sUmod) levels. sUmod, interleukin-1beta (IL-1β), IL-6, IL-10, caspase7, caspase9, tumor necrosis factor-alpha (TNF-α), Bax, and Bcl-xL expression was detected by western blot. Bioinformatics database was used for target prediction and miR-505-5's target was determined by luciferase reporter gene assay.
Results
Relative to sham group, sUmod was highly expressed within myocardial I/R injury (MIRI), whereas sUmod silencing significantly decreased the heart weight/body weight ratio, reduced serum myocardial enzymes expression, ameliorated I/R-mediated myocardial apoptosis, and inflammation. TargetScan bioinformatics database and luciferase reporter genes confirmed that sUmod was miR-505-5p's direct target gene, besides, miR-505-5p overexpression significantly improved the myocardial injury score, increased IL-10, decreased TNF-α, IL-1β, IL-6 expression, decreased caspase7, caspase9, Bax expression, and increased Bcl-xL expression. More importantly, overexpression of sUmod abolished miR-505-5p overexpression's role in I/R-mediated myocardial apoptosis and inflammation.