Progranulin mitigates intestinal injury in a murine model of necrotizing enterocolitis by suppressing M1 macrophage polarization

Abstract

AbstractNeonatal necrotizing enterocolitis (NEC) is a critical digestive disorder frequently affecting premature infants. Characterized by intestinal inflammation caused by activated M1 macrophages, modulation of macrophage polarization is considered a promising therapeutic strategy for NEC. It has been demonstrated that the growth factor‐like protein progranulin (PGRN), which plays roles in a number of physiological and pathological processes, can influence macrophage polarization and exhibit anti‐inflammatory characteristics in a number of illnesses. However, its role in NEC is yet to be investigated. Our research showed that the levels of PGRN were markedly elevated in both human and animal models of NEC. PGRN deletion in mice worsens NEC by encouraging M1 polarization of macrophages and escalating intestinal damage and inflammation. Intravenous administration of recombinant PGRN to NEC mice showed significant survival benefits and protective effects, likely due to PGRN's ability to inhibit M1 polarization and reduce the release of pro‐inflammatory factors. Our findings shed new light on PGRN's biological role in NEC and demonstrate its potential as a therapeutic target for the disease.