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Acceleration of TAA-Induced Liver Fibrosis by Stress Exposure Is Associated with Upregulation of Nerve Growth Factor and Glycopattern Deviations

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 l...

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Autores principales: Atorrasagasti, Catalina, Piccioni, Flavia, Borowski, Sophia, Tirado-González, Irene, Freitag, Nancy, Cantero, María José, Bayo, Juan, Mazzolini, Guillermo, Alaniz, Laura D., Blois, Sandra M., Garcia, Mariana G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8151393/
https://www.ncbi.nlm.nih.gov/pubmed/34064584
http://dx.doi.org/10.3390/ijms22105055
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author Atorrasagasti, Catalina
Piccioni, Flavia
Borowski, Sophia
Tirado-González, Irene
Freitag, Nancy
Cantero, María José
Bayo, Juan
Mazzolini, Guillermo
Alaniz, Laura D.
Blois, Sandra M.
Garcia, Mariana G.
author_facet Atorrasagasti, Catalina
Piccioni, Flavia
Borowski, Sophia
Tirado-González, Irene
Freitag, Nancy
Cantero, María José
Bayo, Juan
Mazzolini, Guillermo
Alaniz, Laura D.
Blois, Sandra M.
Garcia, Mariana G.
author_sort Atorrasagasti, Catalina
collection PubMed
description 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 β1,6GlcNAc-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.
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spelling pubmed-81513932021-05-27 Acceleration of TAA-Induced Liver Fibrosis by Stress Exposure Is Associated with Upregulation of Nerve Growth Factor and Glycopattern Deviations Atorrasagasti, Catalina Piccioni, Flavia Borowski, Sophia Tirado-González, Irene Freitag, Nancy Cantero, María José Bayo, Juan Mazzolini, Guillermo Alaniz, Laura D. Blois, Sandra M. Garcia, Mariana G. Int J Mol Sci Article 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 β1,6GlcNAc-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. MDPI 2021-05-11 /pmc/articles/PMC8151393/ /pubmed/34064584 http://dx.doi.org/10.3390/ijms22105055 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Atorrasagasti, Catalina
Piccioni, Flavia
Borowski, Sophia
Tirado-González, Irene
Freitag, Nancy
Cantero, María José
Bayo, Juan
Mazzolini, Guillermo
Alaniz, Laura D.
Blois, Sandra M.
Garcia, Mariana G.
Acceleration of TAA-Induced Liver Fibrosis by Stress Exposure Is Associated with Upregulation of Nerve Growth Factor and Glycopattern Deviations
title Acceleration of TAA-Induced Liver Fibrosis by Stress Exposure Is Associated with Upregulation of Nerve Growth Factor and Glycopattern Deviations
title_full Acceleration of TAA-Induced Liver Fibrosis by Stress Exposure Is Associated with Upregulation of Nerve Growth Factor and Glycopattern Deviations
title_fullStr Acceleration of TAA-Induced Liver Fibrosis by Stress Exposure Is Associated with Upregulation of Nerve Growth Factor and Glycopattern Deviations
title_full_unstemmed Acceleration of TAA-Induced Liver Fibrosis by Stress Exposure Is Associated with Upregulation of Nerve Growth Factor and Glycopattern Deviations
title_short Acceleration of TAA-Induced Liver Fibrosis by Stress Exposure Is Associated with Upregulation of Nerve Growth Factor and Glycopattern Deviations
title_sort acceleration of taa-induced liver fibrosis by stress exposure is associated with upregulation of nerve growth factor and glycopattern deviations
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8151393/
https://www.ncbi.nlm.nih.gov/pubmed/34064584
http://dx.doi.org/10.3390/ijms22105055
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