PHARMACEUTICAL COMPOSITION FOR TREATING MYOCARDIAL DAMAGE, PHARMACEUTICAL COMPOSITION FOR PREVENTING MYOCARDIAL DAMAGE, PHARMACEUTICAL COMPOSITION FOR TREATING HEART FAILURE, PHARMACEUTICAL COMPOSITION FOR PREVENTING HEART FAILURE, METHOD FOR TREATING OR PREVENTING MYOCARDIAL DAMAGE OR HEART FAILURE, MFG-E8, USES OF MFG-E8, AND METHOD FOR SCREENING COMPOUNDS FOR TREATING OR PREVENTING MYOCARDIAL DAMAGE OR HEART FAILURE

摘要

MFG-E8 is produced by myofibroblasts appearing in an infarct region. The production of MFG-E8 is regulated by TGF-β/SRF signals. Myofibroblasts ingest dead cells through MFG-E8, inducing an anti-inflammatory response due to phagocytosis by such macrophages. Consequently, in MFG-E8-deficient mice, many more apoptotic cells remain in an infarct region of the heart without undergoing phagocytosis, causing excessive inflammation in said region. As a result, the survival rate of MFG-E8-deficient mice after myocardial infarction decreases significantly. Conversely, the removal of apoptotic cells is facilitated by injecting MFG-E8 into the infarct region, alleviating inflammation in the infarct region, resulting in a marked improvement in cardiac function after a myocardial infarction. These findings indicate that MFG-E8 may provide a novel treatment target for the treatment of myocardial infarctions.