{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T20:54:46Z","timestamp":1776459286972,"version":"3.51.2"},"reference-count":56,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,5,11]],"date-time":"2021-05-11T00:00:00Z","timestamp":1620691200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deutsche Forschungsgemeinschaft","award":["BL1115\/7-1"],"award-info":[{"award-number":["BL1115\/7-1"]}]},{"DOI":"10.13039\/100005156","name":"Alexander von Humboldt-Stiftung","doi-asserted-by":"publisher","award":["ARG\/1128984"],"award-info":[{"award-number":["ARG\/1128984"]}],"id":[{"id":"10.13039\/100005156","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Liver fibrosis results from many chronic injuries and may often progress to cirrhosis and hepatocellular carcinoma (HCC). In fact, up to 90% of HCC arise in a cirrhotic liver. Conversely, stress is implicated in liver damage, worsening disease outcome. Hence, stress could play a role in disrupting liver homeostasis, a concept that has not been fully explored. Here, in a murine model of TAA-induced liver fibrosis we identified nerve growth factor (NGF) to be a crucial regulator of the stress-induced fibrogenesis signaling pathway as it activates its receptor p75 neurotrophin receptor (p75NTR), increasing liver damage. Additionally, blocking the NGF decreased liver fibrosis whereas treatment with recombinant NGF accelerated the fibrotic process to a similar extent than stress challenge. We further show that the fibrogenesis induced by stress is characterized by specific changes in the hepatoglycocode (increased \u03b21,6GlcNAc-branched complex N-glycans and decreased core 1 O-glycans expression) which are also observed in patients with advanced fibrosis compared to patients with a low level of fibrosis. Our study facilitates an understanding of stress-induced liver injury and identify NGF signaling pathway in early stages of the disease, which contributes to the established fibrogenesis.<\/jats:p>","DOI":"10.3390\/ijms22105055","type":"journal-article","created":{"date-parts":[[2021,5,11]],"date-time":"2021-05-11T04:05:32Z","timestamp":1620705932000},"page":"5055","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Acceleration of TAA-Induced Liver Fibrosis by Stress Exposure Is Associated with Upregulation of Nerve Growth Factor and Glycopattern Deviations"],"prefix":"10.3390","volume":"22","author":[{"given":"Catalina","family":"Atorrasagasti","sequence":"first","affiliation":[{"name":"Instituto de Investigaciones en Medicina Traslacional, Facultad de Ciencias Biom\u00e9dicas, CONICET, Universidad Austral, Derqui-Pilar B1629, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Flavia","family":"Piccioni","sequence":"additional","affiliation":[{"name":"Laboratorio de Oncolog\u00eda Molecular y Nuevos Blancos Terap\u00e9uticos, Instituto de Biolog\u00eda y Medicina Experimental (IBYME), CONICET, Buenos Aires C1428, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9972-8389","authenticated-orcid":false,"given":"Sophia","family":"Borowski","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Fetal Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"},{"name":"Experimental and Clinical Research Center, a Cooperation between the Max Delbr\u00fcck Center for Molecular Medicine in the Helmholtz Association, and the Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, AG GlycoImmunology, 13125 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irene","family":"Tirado-Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Experimental and Clinical Research Center, a Cooperation between the Max Delbr\u00fcck Center for Molecular Medicine in the Helmholtz Association, and the Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, AG GlycoImmunology, 13125 Berlin, Germany"},{"name":"Georg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy, 60596 Frankfurt, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5972-1863","authenticated-orcid":false,"given":"Nancy","family":"Freitag","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Fetal Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"},{"name":"Experimental and Clinical Research Center, a Cooperation between the Max Delbr\u00fcck Center for Molecular Medicine in the Helmholtz Association, and the Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, AG GlycoImmunology, 13125 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda Jos\u00e9","family":"Cantero","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones en Medicina Traslacional, Facultad de Ciencias Biom\u00e9dicas, CONICET, Universidad Austral, Derqui-Pilar B1629, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan","family":"Bayo","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones en Medicina Traslacional, Facultad de Ciencias Biom\u00e9dicas, CONICET, Universidad Austral, Derqui-Pilar B1629, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guillermo","family":"Mazzolini","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones en Medicina Traslacional, Facultad de Ciencias Biom\u00e9dicas, CONICET, Universidad Austral, Derqui-Pilar B1629, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6070-6078","authenticated-orcid":false,"given":"Laura D.","family":"Alaniz","sequence":"additional","affiliation":[{"name":"Laboratorio de Microambiente Tumoral, Centro de Investigaciones B\u00e1sicas y Aplicadas (CIBA), Centro de Investigaciones y Transferencia del Noroeste de la Pcia. de Bs. As. (CIT NOBA UNNOBA-CONICET), Universidad Nacional del Noroeste de la Pcia. de Bs. As., Jun\u00edn B6000, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0434-2660","authenticated-orcid":false,"given":"Sandra M.","family":"Blois","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Fetal Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8999-5347","authenticated-orcid":false,"given":"Mariana G.","family":"Garcia","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones en Medicina Traslacional, Facultad de Ciencias Biom\u00e9dicas, CONICET, Universidad Austral, Derqui-Pilar B1629, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.addr.2017.05.007","article-title":"Hepatic stellate cells as key target in liver fibrosis","volume":"121","author":"Higashi","year":"2017","journal-title":"Adv. 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