Abstract：
Neonatal 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.
摘要：
新生儿坏死性小肠结肠炎（NEC）是一种严重的消化系统疾病，经常影响早产儿。以活化的M1巨噬细胞引起的肠道炎症为特征，调节巨噬细胞极化被认为是NEC的有前途的治疗策略。已经证明，生长因子样蛋白颗粒蛋白前体（PGRN），在许多生理和病理过程中发挥作用，可以影响巨噬细胞极化并在许多疾病中表现出抗炎特性。然而,它在NEC中的作用还有待调查。我们的研究表明，在NEC的人类和动物模型中，PGRN的水平均显着升高。小鼠中的PGRN缺失通过促进巨噬细胞的M1极化以及不断升级的肠损伤和炎症而使NEC恶化。对NEC小鼠静脉给予重组PGRN显示出显著的存活益处和保护作用,可能是由于PGRN抑制M1极化和减少促炎因子释放的能力。我们的发现为PGRN在NEC中的生物学作用提供了新的思路，并证明了其作为该疾病治疗靶点的潜力。
