{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T22:44:42Z","timestamp":1788389082532,"version":"build-2803163510"},"reference-count":55,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,5,26]],"date-time":"2025-05-26T00:00:00Z","timestamp":1748217600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["No. 82270680, 82200721, 82300732"],"award-info":[{"award-number":["No. 82270680, 82200721, 82300732"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018541","name":"Science Fund for Distinguished Young Scholars of Jiangsu Province","doi-asserted-by":"publisher","award":["No. BK20240028"],"award-info":[{"award-number":["No. BK20240028"]}],"id":[{"id":"10.13039\/501100018541","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Macrophage activation is closely associated with Acute pancreatitis (AP). We screened and found that Growth factor receptor bound protein 2 (Grb2) is highly expressed in macrophages during AP. However, the relationship between Grb2 and AP is still poorly understood. In this study, we explored the role of Grb2 in AP.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We screened for gene affecting macrophage activation in AP by combining transcriptomics with Single-cell RNA-sequence analysis. Next, the expression of Grb2 in M1\/M2 macrophage activation was detected by Single-cell RNA-sequence analysis and western blot. Furthermore, the effect of Grb2 on M1\/M2 macrophage activation was detected by flow cytometry. The severity of AP was assessed by histological analysis, serum amylase, serum lipase and serum inflammatory factors <jats:italic>in vivo<\/jats:italic>. NOD-like receptor thermal protein domain associated protein 3 (Nlrp3) and Nuclear factor kappa-B (NF-kB) signaling pathways were also evaluated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Grb2 is mainly expressed in macrophages of pancreas in AP and up-regulated in M1 macrophage activation. Inhibiting Grb2 could alleviate AP by preventing M1 macrophage activation through down-regulating Nlrp3 and NF-\u03baB.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Inhibition of Grb2 can effectively prevent M1 macrophage activation and alleviate AP. Grb2 may potentially be an effective target of macrophage activation for the treatment of AP.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1575880","type":"journal-article","created":{"date-parts":[[2025,5,26]],"date-time":"2025-05-26T04:10:40Z","timestamp":1748232640000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Identification of Grb2 protein as a potential mediator of macrophage activation in acute pancreatitis based on bioinformatics and experimental 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