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Autophagy and Exosomes: Cross-Regulated Pathways Playing Major Roles in Hepatic Stellate Cells Activation and Liver Fibrosis

Chronic liver injury, regardless of the underlying disease, results in gradual alteration of the physiological hepatic architecture and in excessive production of extracellular matrix, eventually leading to cirrhosis Liver cellular architecture consists of different cell populations, among which hep...

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Autores principales: Mastoridou, Eleftheria M., Goussia, Anna C., Glantzounis, Georgios K., Kanavaros, Panagiotis, Charchanti, Antonia V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8850693/
https://www.ncbi.nlm.nih.gov/pubmed/35185602
http://dx.doi.org/10.3389/fphys.2021.801340
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author Mastoridou, Eleftheria M.
Goussia, Anna C.
Glantzounis, Georgios K.
Kanavaros, Panagiotis
Charchanti, Antonia V.
author_facet Mastoridou, Eleftheria M.
Goussia, Anna C.
Glantzounis, Georgios K.
Kanavaros, Panagiotis
Charchanti, Antonia V.
author_sort Mastoridou, Eleftheria M.
collection PubMed
description Chronic liver injury, regardless of the underlying disease, results in gradual alteration of the physiological hepatic architecture and in excessive production of extracellular matrix, eventually leading to cirrhosis Liver cellular architecture consists of different cell populations, among which hepatic stellate cells (HSCs) have been found to play a major role in the fibrotic process. Under normal conditions, HSCs serve as the main storage site for vitamin A, however, pathological stimuli lead to their transdifferentiation into myofibroblast cells, with autophagy being the key regulator of their activation, through lipophagy of their lipid droplets. Nevertheless, the role of autophagy in liver fibrosis is multifaceted, as increased autophagic levels have been associated with alleviation of the fibrotic process. In addition, it has been found that HSCs receive paracrine stimuli from neighboring cells, such as injured hepatocytes, Kupffer cells, sinusoidal endothelial cells, which promote liver fibrosis. These stimuli have been found to be transmitted via exosomes, which are incorporated by HSCs and can either be degraded through lysosomes or be secreted back into the extracellular space via fusion with the plasma membrane. Furthermore, it has been demonstrated that autophagy and exosomes may be concomitantly or reciprocally regulated, depending on the cellular conditions. Given that increased levels of autophagy are required to activate HSCs, it is important to investigate whether autophagy levels decrease at later stages of hepatic stellate cell activation, leading to increased release of exosomes and further propagation of hepatic fibrosis.
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spelling pubmed-88506932022-02-18 Autophagy and Exosomes: Cross-Regulated Pathways Playing Major Roles in Hepatic Stellate Cells Activation and Liver Fibrosis Mastoridou, Eleftheria M. Goussia, Anna C. Glantzounis, Georgios K. Kanavaros, Panagiotis Charchanti, Antonia V. Front Physiol Physiology Chronic liver injury, regardless of the underlying disease, results in gradual alteration of the physiological hepatic architecture and in excessive production of extracellular matrix, eventually leading to cirrhosis Liver cellular architecture consists of different cell populations, among which hepatic stellate cells (HSCs) have been found to play a major role in the fibrotic process. Under normal conditions, HSCs serve as the main storage site for vitamin A, however, pathological stimuli lead to their transdifferentiation into myofibroblast cells, with autophagy being the key regulator of their activation, through lipophagy of their lipid droplets. Nevertheless, the role of autophagy in liver fibrosis is multifaceted, as increased autophagic levels have been associated with alleviation of the fibrotic process. In addition, it has been found that HSCs receive paracrine stimuli from neighboring cells, such as injured hepatocytes, Kupffer cells, sinusoidal endothelial cells, which promote liver fibrosis. These stimuli have been found to be transmitted via exosomes, which are incorporated by HSCs and can either be degraded through lysosomes or be secreted back into the extracellular space via fusion with the plasma membrane. Furthermore, it has been demonstrated that autophagy and exosomes may be concomitantly or reciprocally regulated, depending on the cellular conditions. Given that increased levels of autophagy are required to activate HSCs, it is important to investigate whether autophagy levels decrease at later stages of hepatic stellate cell activation, leading to increased release of exosomes and further propagation of hepatic fibrosis. Frontiers Media S.A. 2022-02-03 /pmc/articles/PMC8850693/ /pubmed/35185602 http://dx.doi.org/10.3389/fphys.2021.801340 Text en Copyright © 2022 Mastoridou, Goussia, Glantzounis, Kanavaros and Charchanti. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Physiology
Mastoridou, Eleftheria M.
Goussia, Anna C.
Glantzounis, Georgios K.
Kanavaros, Panagiotis
Charchanti, Antonia V.
Autophagy and Exosomes: Cross-Regulated Pathways Playing Major Roles in Hepatic Stellate Cells Activation and Liver Fibrosis
title Autophagy and Exosomes: Cross-Regulated Pathways Playing Major Roles in Hepatic Stellate Cells Activation and Liver Fibrosis
title_full Autophagy and Exosomes: Cross-Regulated Pathways Playing Major Roles in Hepatic Stellate Cells Activation and Liver Fibrosis
title_fullStr Autophagy and Exosomes: Cross-Regulated Pathways Playing Major Roles in Hepatic Stellate Cells Activation and Liver Fibrosis
title_full_unstemmed Autophagy and Exosomes: Cross-Regulated Pathways Playing Major Roles in Hepatic Stellate Cells Activation and Liver Fibrosis
title_short Autophagy and Exosomes: Cross-Regulated Pathways Playing Major Roles in Hepatic Stellate Cells Activation and Liver Fibrosis
title_sort autophagy and exosomes: cross-regulated pathways playing major roles in hepatic stellate cells activation and liver fibrosis
topic Physiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8850693/
https://www.ncbi.nlm.nih.gov/pubmed/35185602
http://dx.doi.org/10.3389/fphys.2021.801340
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