{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T07:56:31Z","timestamp":1774857391433,"version":"3.50.1"},"reference-count":37,"publisher":"Portland Press Ltd.","issue":"9","license":[{"start":{"date-parts":[[2022,4,19]],"date-time":"2022-04-19T00:00:00Z","timestamp":1650326400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,5,13]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Annexin A1 (AnxA1) is an important effector in the resolution of inflammation which is involved in modulating hepatic inflammation in nonalcoholic steatohepatitis (NASH). In the present study, we have investigated the possible effects of treatment with AnxA1 for counteracting the progression of experimental NASH.<\/jats:p>\n               <jats:p>NASH was induced in C57BL\/6 mice by feeding methionine\u2013choline deficient (MCD) or Western diets (WDs) and the animals were treated for 4\u20136 weeks with human recombinant AnxA1 (hrAnxA1; 1 \u00b5g, daily IP) or saline once NASH was established.<\/jats:p>\n               <jats:p>In both experimental models, treatment with hrAnxA1 improved parenchymal injury and lobular inflammation without interfering with the extension of steatosis. Furthermore, administration of hrAnxA1 significantly attenuated the hepatic expression of \u03b11-procollagen and TGF-\u03b21 and reduced collagen deposition, as evaluated by collagen Sirius Red staining. Flow cytometry and immunohistochemistry showed that hrAnxA1 did not affect the liver recruitment of macrophages, but strongly interfered with the formation of crown-like macrophage aggregates and reduced their capacity of producing pro-fibrogenic mediators like osteopontin (OPN) and galectin-3 (Gal-3). This effect was related to an interference with the acquisition of a specific macrophage phenotype characterized by the expression of the Triggering Receptor Expressed on Myeloid cells 2 (TREM-2), CD9 and CD206, previously associated with NASH evolution to cirrhosis.<\/jats:p>\n               <jats:p>Collectively, these results indicate that, beside ameliorating hepatic inflammation, AnxA1 is specifically effective in preventing NASH-associated fibrosis by interfering with macrophage pro-fibrogenic features. Such a novel function of AnxA1 gives the rationale for the development of AnxA1 analogs for the therapeutic control of NASH evolution.<\/jats:p>","DOI":"10.1042\/cs20211122","type":"journal-article","created":{"date-parts":[[2022,4,19]],"date-time":"2022-04-19T10:15:37Z","timestamp":1650363337000},"page":"643-656","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Annexin A1 treatment prevents the evolution to fibrosis of experimental nonalcoholic steatohepatitis"],"prefix":"10.1042","volume":"136","author":[{"given":"Laila\u00a0Lavanya","family":"Gadipudi","sequence":"first","affiliation":[{"name":"Department of Health Sciences and Interdisciplinary Research Centre for Autoimmune Diseases, University of East Piedmont, Novara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naresh\u00a0Naik","family":"Ramavath","sequence":"additional","affiliation":[{"name":"Department of Health Sciences and Interdisciplinary Research Centre for Autoimmune Diseases, University of East Piedmont, Novara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessia","family":"Provera","sequence":"additional","affiliation":[{"name":"Department of Health Sciences and Interdisciplinary Research Centre for Autoimmune Diseases, University of East Piedmont, Novara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chris","family":"Reutelingsperger","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Institute Maastricht, Department of Biochemistry, Maastricht University, Maastricht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4738-7049","authenticated-orcid":false,"given":"Emanuele","family":"Albano","sequence":"additional","affiliation":[{"name":"Department of Health Sciences and Interdisciplinary Research Centre for Autoimmune Diseases, University of East Piedmont, Novara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mauro","family":"Perretti","sequence":"additional","affiliation":[{"name":"William Harvey Research Institute, Barts and The London School of Medicine, Queen Mary University of London, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Salvatore","family":"Sutti","sequence":"additional","affiliation":[{"name":"Department of Health Sciences and Interdisciplinary Research Centre for Autoimmune Diseases, University of East Piedmont, Novara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","published-online":{"date-parts":[[2022,5,4]]},"reference":[{"key":"2022050408061022400_B1","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1038\/nrgastro.2017.109","article-title":"Global burden of NAFLD and NASH: trends, predictions, risk factors and prevention","volume":"15","author":"Younossi","year":"2018","journal-title":"Nat. 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