Cargando…
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...
Autores principales: | , , , , , , , , , , |
---|---|
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 |
_version_ | 1783698372302995456 |
---|---|
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. |
format | Online Article Text |
id | pubmed-8151393 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT atorrasagasticatalina accelerationoftaainducedliverfibrosisbystressexposureisassociatedwithupregulationofnervegrowthfactorandglycopatterndeviations AT piccioniflavia accelerationoftaainducedliverfibrosisbystressexposureisassociatedwithupregulationofnervegrowthfactorandglycopatterndeviations AT borowskisophia accelerationoftaainducedliverfibrosisbystressexposureisassociatedwithupregulationofnervegrowthfactorandglycopatterndeviations AT tiradogonzalezirene accelerationoftaainducedliverfibrosisbystressexposureisassociatedwithupregulationofnervegrowthfactorandglycopatterndeviations AT freitagnancy accelerationoftaainducedliverfibrosisbystressexposureisassociatedwithupregulationofnervegrowthfactorandglycopatterndeviations AT canteromariajose accelerationoftaainducedliverfibrosisbystressexposureisassociatedwithupregulationofnervegrowthfactorandglycopatterndeviations AT bayojuan accelerationoftaainducedliverfibrosisbystressexposureisassociatedwithupregulationofnervegrowthfactorandglycopatterndeviations AT mazzoliniguillermo accelerationoftaainducedliverfibrosisbystressexposureisassociatedwithupregulationofnervegrowthfactorandglycopatterndeviations AT alanizlaurad accelerationoftaainducedliverfibrosisbystressexposureisassociatedwithupregulationofnervegrowthfactorandglycopatterndeviations AT bloissandram accelerationoftaainducedliverfibrosisbystressexposureisassociatedwithupregulationofnervegrowthfactorandglycopatterndeviations AT garciamarianag accelerationoftaainducedliverfibrosisbystressexposureisassociatedwithupregulationofnervegrowthfactorandglycopatterndeviations |