Deletion of ASPP1 in myofibroblasts alleviates myocardial fibrosis by reducing p53 degradation

In this study, we revealed an unexpected phenomenon that is completely different from what observed in cancer cells and cardiomyocytes, ASPP1 negatively regulates p53 level in cardiac fibroblasts and promotes its proliferation. The mechanism is that ASPP1 inhibits p53 deubiquitination by binding to the deubiquitinating protein OTUB1, and thus promotes p53 ubiquitination and degradation. We also demonstrated that inhibition of ASPP1 in myofibroblasts can significantly alleviate myocardial fibrosis caused by chronic myocardial infarction. ASPP1 represents a novel target for the development of strategy against post-infarct remodeling and cardiac sudden death associated with heart failure. Our previous and the current studies indicate that inhibition of ASPP1 is beneficial to the ischemic injured hearts due to the prevention of cardiomyocyte apoptosis and cardiac fibroblast activation.