Ring Finger Protein 4 alleviates inflammation of heart after myocardial infarction by suppressing MAPK signaling via TAK1

  AIM  To investigate the roles of Ring Finger Protein 4(RNF4) in inflammation of heart after myocardial infarction (MI) and its potential mechanism

  Methods  Mice with cardiac-specific over-expression of RNF4 and C57 mice were subjected to myocardial infarction operation and their death rate was recorded respectively. Hearts were harvested at 28 days and then HE staining, qPCR and Western blot were performed to determine the roles of RNF4 over-expression in inflammation after myocardial infarction and its underlying mechanism. Co-immunoprecipitation (Co-IP) was used to explore the potential protein which can interact with RNF4 and its exact interacting domain.

  RESULTS  In MI model, both protein and mRNA levels of RNF4 decreased in MI mice compared with those in untreated mice (P<0.05). The mice with cardiac-specific over-expression of RNF4 had a lower death rate and a mild inflammatory response characterized by a less infiltration of leukomonocytes in myocardial matrix, compared with C57 mice. The results of Western blot showed that RNF4 mitigated inflammation by suppressing MAPK signaling after MI. Subsequently, the results of Co-IP identified that RNF4 recruited and degraded TAK1. It was found that RNF4 bound the exact domain from 301st amino acid to the 480th amino acid of TAK1.

  CONCLUSION  RNF4 reduces the inflammatory responses and mortality after myocardial infarction by suppressing MAPK signaling through recruiting and degrading TAK1. RNF4 is a potential target to improve the prognosis of myocardial infarction, which is of great clinical significance.