{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T22:24:28Z","timestamp":1769034268719,"version":"3.49.0"},"update-to":[{"DOI":"10.1371\/journal.pntd.0013497","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T00:00:00Z","timestamp":1768867200000}}],"reference-count":46,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T00:00:00Z","timestamp":1768262400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key R&D Program of China","doi-asserted-by":"crossref","award":["2024YFC2309700"],"award-info":[{"award-number":["2024YFC2309700"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"crossref"}]},{"name":"General Program of National Natural Science Foundation of China","award":["82573336"],"award-info":[{"award-number":["82573336"]}]},{"name":"Corps Guidance Science and Technology Plan Project","award":["2024ZD018"],"award-info":[{"award-number":["2024ZD018"]}]},{"name":"Corps Guidance Science and Technology Plan Project","award":["2023ZD034"],"award-info":[{"award-number":["2023ZD034"]}]},{"name":"Tianshan Young Talent Scientific and Technological Innovation Team","award":["2023TSYCTD0020"],"award-info":[{"award-number":["2023TSYCTD0020"]}]},{"name":"Shihezi University Scientific Research Project","award":["ZZZC2023026"],"award-info":[{"award-number":["ZZZC2023026"]}]}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The SUMOylation modification is closely linked to the progression of fibrotic diseases, yet its role in hepatic fibrosis associated with cystic echinococcosis (CE) remains unclear. This study aimed to investigate the function of SUMOylation in CE-related hepatic fibrosis and evaluate the anti-fibrotic effects and mechanisms of ginkgolic acid (GA) via regulation of the SUMOylation pathway.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methodology<\/jats:title>\n                    <jats:p>\n                      Peri-lesional (PL) and adjacent normal (AN) liver tissues from CE patients were collected to examine histopathology and SUMO pathway proteins. A CE-infected mouse model was established and treated with GA to assess cyst burden, serum TGF-\u03b21 levels, hepatic fibrosis markers, and SUMO-related proteins.\n                      <jats:italic>In vitro<\/jats:italic>\n                      , macrophages and hepatic stellate cells (HSCs, LX-2 line) were stimulated with\n                      <jats:italic>Echinococcus granulosus<\/jats:italic>\n                      cyst fluid (EgCF) or TGF-\u03b21 to evaluate GA\u2019s effects on macrophage polarization (CD206\/CD86), HSC activation (\u03b1-SMA\/PCNA), Smad4 SUMOylation, and nuclear translocation. Macrophage-HSC crosstalk was investigated via conditioned medium co-culture assays.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Result<\/jats:title>\n                    <jats:p>Fibrosis was exacerbated in peri-lesional liver tissues of CE patients, accompanied by SUMO pathway activation. GA significantly alleviated hepatic fibrosis in CE mice and reversed SUMO pathway dysregulation. Mechanistically, GA inhibited EgCF-induced pro-fibrotic M2 macrophage polarization and blocked Smad4 SUMOylation and nuclear translocation by modulating SUMOylation. Furthermore, GA directly suppressed HSC activation and bidirectionally disrupted the pro-fibrotic crosstalk between macrophages and HSCs under EgCF stimulation, ultimately alleviating fibrosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study reveals the critical role of SUMOylation modification in CE-associated hepatic fibrosis and elucidates a novel anti-fibrotic mechanism whereby GA targets the SUMOylation-Smad4 axis to regulate the immune microenvironment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pntd.0013497","type":"journal-article","created":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T18:40:52Z","timestamp":1768329652000},"page":"e0013497","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Ginkgolic acid attenuates echinococcus 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