Conclusion
EXE can modulate the miR-30d-5p/GALNT7 axis to inhibit the expression of TSHR, thereby regulating the polarization of macrophages to the M2 phenotype and ultimately alleviating DOX-induced myocardial injury, which provides new targets and strategies for the clinical treatment of myocardial injury.
Methods
In this study, cell and animal models of DOX-induced myocardial injury were constructed. The animal model was subjected to EXE intervention.
Objective
Doxorubicin (DOX) is an extensively used chemotherapeutic agent that induces cardiotoxicity. Studies have reported that exercise (EXE) can alleviate DOX-induced cardiotoxicity. Therefore, this study aimed to explore the mechanism by which EXE attenuates DOX-induced myocardial injury.
Results
In this study, in vitro experiments revealed that miR-30d-5p negatively regulated polypeptide N-acetylgalactosaminyltransferase 7 (GALNT7) and that GALNT7 negatively regulated the expression of thyroid stimulating hormone receptor (TSHR). miR-30d-5p downregulated the expression of GALNT7, promoted the expression of TSHR, and promoted macrophage M1 polarization, thus aggravating cardiomyocyte injury. In vivo experiments revealed that EXE intervention significantly downregulated miR-30d-5p and TSHR expression, upregulated GALNT7, reduced inflammation, and promoted M2 macrophage polarization, thereby alleviating DOX-induced myocardial injury. In addition, overexpression of miR-30d-5p or knockdown of GALNT7 weakened the intervention effect of EXE, whereas overexpression of GALNT7 or knockdown of TSHR promoted the effect of EXE.