An increase in microRNA‐23 prevents muscle wasting in mice with chronic kidney disease in resistance exercise (731.8)

Abstract

In our previous studies we found that exercise partially prevents chronic kidney disease (CKD)‐induced muscle atrophy. We also saw that microRNA‐23 (miR‐23) is decreased in muscles of CKD mice. In silico analysis suggested that miR‐23 targets several proteins associated with muscle atrophy. In this study, we evaluated whether exercise restores the level of miR‐23 in CKD mice. CKD was induced in 20‐25g mice by 5/6th nephrectomy. Muscle overloading, a resistance exercise model, was produced in both control and CKD mice by removing the gastrocnemius and soleus muscles from both hindlimbs. Overexpression of miR‐23 in cultured muscle cells inhibits the reporter luciferase activities of PTEN and YY1, suggesting that miR‐23 attenuates the expression of these predicted targets. Exercise significantly increased the level of miR‐23 in muscle of CKD mice vs. unexercised CKD mice. Consistent with this, exercise decreased PTEN protein and increased consequent Akt phosphorylation (2.3‐fold, P<0.001) which would limit muscle atrophy. In CKD mice, exercise increased MyoD, myogenin and eMyHC, proteins that are linked to the myogenic transcription factor, YY1. Conclusions: Resistance exercise can increase miR‐23 which leads to a suppression of multiple atrophy‐related target proteins that may contribute to the muscle‐sparing effects of exercise in CKD.Grant Funding Source: NIH AR060268 (XHW)