ZNF143 regulates autophagic flux to alleviate myocardial ischemia/reperfusion injury through Raptor.

The exact role of autophagy in myocardial ischemia/reperfusion (I/R) injury is still controversial. Excessive or insufficient autophagy may lead to cell death. Therefore, how to regulate autophagic balance during myocardial ischemia/reperfusion is critical to the treatment of myocardial I/R injury. Raptor is an mTOR regulatory related protein and closely related to the induction of autophagy. ZNF143 is widely expressed in various cells and acts as a transcription factor, which is involved in the regulation of autophagy, cell growth and development. In this study, we aimed to explore the mechanism by which ZNF143 regulated autophagy in myocardial I/R injury and the relationship between ZNF143 and Raptor. In our results, we found that ZNF143 expression was down-regulated in myocardial I/R. Inhibition of ZNF143 expression further enhanced autophagy and restored the deficiency of autophagic flux caused by myocardial I/R, subsequently alleviating myocardial I/R injury. On the other hand, overexpression of ZNF143 up-regulated Raptor expression and reduced autophagic activity, consequently exacerbating myocardial I/R injury. Taken together, our study revealed that ZNF143 might be a key target of the regulation of autophagy and a novel therapeutic target of myocardial I/R injury.