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

IF 3.3 3区生物学 Q3 CELL BIOLOGY

Cell Biology International Pub Date : 2024-07-08 DOI:10.1002/cbin.12209

Dandan Mo, Youjun Qiu, Bing Tian, Xinli Liu, Yujie Chen, Guotao Zou, Chunbao Guo, Chun Deng

{"title":"Progranulin mitigates intestinal injury in a murine model of necrotizing enterocolitis by suppressing M1 macrophage polarization","authors":"Dandan Mo, Youjun Qiu, Bing Tian, Xinli Liu, Yujie Chen, Guotao Zou, Chunbao Guo, Chun Deng","doi":"10.1002/cbin.12209","DOIUrl":null,"url":null,"abstract":"<p>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.</p>","PeriodicalId":9806,"journal":{"name":"Cell Biology International","volume":"48 10","pages":"1520-1532"},"PeriodicalIF":3.3000,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell Biology International","FirstCategoryId":"99","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/cbin.12209","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CELL BIOLOGY","Score":null,"Total":0}

引用次数: 0

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.

查看原文本刊更多论文

在小鼠坏死性小肠结肠炎模型中，Progranulin 通过抑制 M1 巨噬细胞极化减轻肠道损伤。

新生儿坏死性小肠结肠炎（NEC）是早产儿常患的一种严重消化系统疾病。其特征是由活化的 M1 巨噬细胞引起的肠道炎症，因此，调节巨噬细胞的极化被认为是治疗 NEC 的一种很有前景的策略。有研究表明，生长因子样蛋白原花青素（PGRN）在多种生理和病理过程中发挥作用，可影响巨噬细胞的极化，并在多种疾病中表现出抗炎特性。然而，它在 NEC 中的作用还有待研究。我们的研究表明，在人类和动物 NEC 模型中，PGRN 的水平都明显升高。在小鼠体内缺失 PGRN 会促使巨噬细胞 M1 极化，加剧肠道损伤和炎症，从而使 NEC 恶化。静脉注射重组 PGRN 对 NEC 小鼠有显著的生存益处和保护作用，这可能是由于 PGRN 能够抑制 M1 极化并减少促炎因子的释放。我们的研究结果揭示了 PGRN 在 NEC 中的生物学作用，并证明了其作为该疾病治疗靶点的潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Cell Biology International 生物-细胞生物学

CiteScore

7.60

自引率

0.00%

发文量

208

审稿时长

1 months

期刊介绍： Each month, the journal publishes easy-to-assimilate, up-to-the minute reports of experimental findings by researchers using a wide range of the latest techniques. Promoting the aims of cell biologists worldwide, papers reporting on structure and function - especially where they relate to the physiology of the whole cell - are strongly encouraged. Molecular biology is welcome, as long as articles report findings that are seen in the wider context of cell biology. In covering all areas of the cell, the journal is both appealing and accessible to a broad audience. Authors whose papers do not appeal to cell biologists in general because their topic is too specialized (e.g. infectious microbes, protozoology) are recommended to send them to more relevant journals. Papers reporting whole animal studies or work more suited to a medical journal, e.g. histopathological studies or clinical immunology, are unlikely to be accepted, unless they are fully focused on some important cellular aspect. These last remarks extend particularly to papers on cancer. Unless firmly based on some deeper cellular or molecular biological principle, papers that are highly specialized in this field, with limited appeal to cell biologists at large, should be directed towards journals devoted to cancer, there being very many from which to choose.