{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T11:23:38Z","timestamp":1778066618955,"version":"3.51.4"},"reference-count":37,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","license":[{"start":{"date-parts":[[2020,4,23]],"date-time":"2020-04-23T00:00:00Z","timestamp":1587600000000},"content-version":"am","delay-in-days":335,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#am"},{"start":{"date-parts":[[2019,5,24]],"date-time":"2019-05-24T00:00:00Z","timestamp":1558656000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2019,5,24]],"date-time":"2019-05-24T00:00:00Z","timestamp":1558656000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:p>The growing burden of liver fibrosis and lack of effective antifibrotic therapies highlight the need for identification of pathways and complementary model systems of hepatic fibrosis. A rare, monogenic disorder in which children with mutations in mannose phosphate isomerase (MPI) develop liver fibrosis led us to explore the function of MPI and mannose metabolism in liver development and adult liver diseases. Herein, analyses of transcriptomic data from three human liver cohorts demonstrate that <jats:italic toggle=\"yes\">MPI<\/jats:italic> gene expression is down\u2010regulated proportionate to fibrosis in chronic liver diseases, including nonalcoholic fatty liver disease and hepatitis B virus. Depletion of MPI in zebrafish liver <jats:italic toggle=\"yes\">in vivo<\/jats:italic> and in human hepatic stellate cell (HSC) lines in culture activates fibrotic responses, indicating that loss of MPI promotes HSC activation. We further demonstrate that mannose supplementation can attenuate HSC activation, leading to reduced fibrogenic activation in zebrafish, culture\u2010activated HSCs, and in ethanol\u2010activated HSCs. <jats:italic toggle=\"yes\">Conclusion:<\/jats:italic> These data indicate the prospect that modulation of mannose metabolism pathways could reduce HSC activation and improve hepatic fibrosis.<\/jats:p>","DOI":"10.1002\/hep.30677","type":"journal-article","created":{"date-parts":[[2019,4,24]],"date-time":"2019-04-24T05:39:55Z","timestamp":1556084395000},"page":"2107-2122","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":30,"title":["Mannose Phosphate Isomerase and Mannose Regulate Hepatic Stellate Cell Activation and Fibrosis in Zebrafish and Humans"],"prefix":"10.1097","volume":"70","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5267-6553","authenticated-orcid":false,"given":"Charles","family":"DeRossi","sequence":"first","affiliation":[{"name":"Department of Pediatrics,Icahn School of Medicine at Mount Sinai,New York,NY"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathryn","family":"Bambino","sequence":"additional","affiliation":[{"name":"Department of Environmental Medicine and Public Health,Icahn School of Medicine at Mount Sinai,New York,NY"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joshua","family":"Morrison","sequence":"additional","affiliation":[{"name":"Department of Pediatrics,Icahn School of Medicine at Mount Sinai,New York,NY"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabel","family":"Sakarin","sequence":"additional","affiliation":[{"name":"Department of Pediatrics,Icahn School of Medicine at Mount Sinai,New York,NY"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlos","family":"Villacorta\u2010Martin","sequence":"additional","affiliation":[{"name":"Center for Regenerative Medicine,Boston University and Boston Medical Center,Boston,MA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Changwen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology and Nutrition,Cincinnati Children\u2019s Hospital Medical Center,Cincinnati,OH"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jillian L.","family":"Ellis","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology and Nutrition,Cincinnati Children\u2019s Hospital Medical Center,Cincinnati,OH"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. Isabel","family":"Fiel","sequence":"additional","affiliation":[{"name":"Department of Pathology,Icahn School of Medicine at Mount Sinai,New York,NY"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Ybanez","sequence":"additional","affiliation":[{"name":"Laboratory of RNA Molecular Biology,Rockefeller University,New York,NY"},{"name":"Division of Liver Diseases, Department of Medicine,Icahn School of Medicine at Mount Sinai,New York,NY"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Youngmin A.","family":"Lee","sequence":"additional","affiliation":[{"name":"Laboratory of RNA Molecular Biology,Rockefeller University,New York,NY"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kuan\u2010lin","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Genetics and Genomic Sciences,Icahn School of Medicine at Mount Sinai,New York,NY"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3784-6363","authenticated-orcid":false,"given":"Chunyue","family":"Yin","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology and Nutrition,Cincinnati Children\u2019s Hospital Medical Center,Cincinnati,OH"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takuya F.","family":"Sakaguchi","sequence":"additional","affiliation":[{"name":"Department of Stem Cell Biology and Regenerative Medicine,Lerner Research Institute, Cleveland Clinic Foundation,Cleveland,OH"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Scott L.","family":"Friedman","sequence":"additional","affiliation":[{"name":"Division of Liver Diseases, Department of Medicine,Icahn School of Medicine at Mount Sinai,New York,NY"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Augusto","family":"Villanueva","sequence":"additional","affiliation":[{"name":"Division of Liver Diseases, Department of Medicine,Icahn School of Medicine at Mount Sinai,New York,NY"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaime","family":"Chu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics,Icahn School of Medicine at Mount Sinai,New York,NY"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","published-online":{"date-parts":[[2019,5,24]]},"reference":[{"key":"hep30677-bib-0001-20241017","doi-asserted-by":"crossref","first-page":"e279","DOI":"10.1542\/peds.2013-2732","article-title":"Successful liver transplantation and long\u2010term follow\u2010up in a patient with MPI\u2010CDG","volume":"134","year":"2014","journal-title":"Pediatrics"},{"key":"hep30677-bib-0002-20241017","doi-asserted-by":"crossref","first-page":"1535","DOI":"10.1086\/301873","article-title":"Phosphomannose isomerase deficiency: a carbohydrate\u2010deficient glycoprotein syndrome with hepatic\u2010intestinal presentation","volume":"62","year":"1998","journal-title":"Am J Hum Genet"},{"key":"hep30677-bib-0003-20241017","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1016\/j.bbadis.2008.11.012","article-title":"The clinical spectrum of phosphomannose isomerase deficiency, with an evaluation of mannose treatment for CDG\u2010Ib","volume":"1792","year":"2009","journal-title":"Biochim Biophys Acta"},{"key":"hep30677-bib-0004-20241017","doi-asserted-by":"crossref","first-page":"1414","DOI":"10.1172\/JCI2350","article-title":"Carbohydrate\u2010deficient glycoprotein syndrome type Ib. 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