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Priming, Triggering, Adaptation and Senescence (PTAS): A Hypothesis for a Common Damage Mechanism of Steatohepatitis
Understanding the pathomechanism of steatohepatitis (SH) is hampered by the difficulty of distinguishing between causes and consequences, by the broad spectrum of aetiologies that can produce the phenotype, and by the long time-span during which SH develops, often without clinical symptoms. We propo...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8624051/ https://www.ncbi.nlm.nih.gov/pubmed/34830427 http://dx.doi.org/10.3390/ijms222212545 |
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author | Abuja, Peter M. Zatloukal, Kurt Denk, Helmut |
author_facet | Abuja, Peter M. Zatloukal, Kurt Denk, Helmut |
author_sort | Abuja, Peter M. |
collection | PubMed |
description | Understanding the pathomechanism of steatohepatitis (SH) is hampered by the difficulty of distinguishing between causes and consequences, by the broad spectrum of aetiologies that can produce the phenotype, and by the long time-span during which SH develops, often without clinical symptoms. We propose that SH develops in four phases with transitions: (i) priming lowers stress defence; (ii) triggering leads to acute damage; (iii) adaptation, possibly associated with cellular senescence, mitigates tissue damage, leads to the phenotype, and preserves liver function at a lower level; (iv) finally, senescence prevents neoplastic transformation but favours fibrosis (cirrhosis) and inflammation and further reduction in liver function. Escape from senescence eventually leads to hepatocellular carcinoma. This hypothesis for a pathomechanism of SH is supported by clinical and experimental observations. It allows organizing the various findings to uncover remaining gaps in our knowledge and, finally, to provide possible diagnostic and intervention strategies for each stage of SH development. |
format | Online Article Text |
id | pubmed-8624051 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-86240512021-11-27 Priming, Triggering, Adaptation and Senescence (PTAS): A Hypothesis for a Common Damage Mechanism of Steatohepatitis Abuja, Peter M. Zatloukal, Kurt Denk, Helmut Int J Mol Sci Hypothesis Understanding the pathomechanism of steatohepatitis (SH) is hampered by the difficulty of distinguishing between causes and consequences, by the broad spectrum of aetiologies that can produce the phenotype, and by the long time-span during which SH develops, often without clinical symptoms. We propose that SH develops in four phases with transitions: (i) priming lowers stress defence; (ii) triggering leads to acute damage; (iii) adaptation, possibly associated with cellular senescence, mitigates tissue damage, leads to the phenotype, and preserves liver function at a lower level; (iv) finally, senescence prevents neoplastic transformation but favours fibrosis (cirrhosis) and inflammation and further reduction in liver function. Escape from senescence eventually leads to hepatocellular carcinoma. This hypothesis for a pathomechanism of SH is supported by clinical and experimental observations. It allows organizing the various findings to uncover remaining gaps in our knowledge and, finally, to provide possible diagnostic and intervention strategies for each stage of SH development. MDPI 2021-11-21 /pmc/articles/PMC8624051/ /pubmed/34830427 http://dx.doi.org/10.3390/ijms222212545 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 | Hypothesis Abuja, Peter M. Zatloukal, Kurt Denk, Helmut Priming, Triggering, Adaptation and Senescence (PTAS): A Hypothesis for a Common Damage Mechanism of Steatohepatitis |
title | Priming, Triggering, Adaptation and Senescence (PTAS): A Hypothesis for a Common Damage Mechanism of Steatohepatitis |
title_full | Priming, Triggering, Adaptation and Senescence (PTAS): A Hypothesis for a Common Damage Mechanism of Steatohepatitis |
title_fullStr | Priming, Triggering, Adaptation and Senescence (PTAS): A Hypothesis for a Common Damage Mechanism of Steatohepatitis |
title_full_unstemmed | Priming, Triggering, Adaptation and Senescence (PTAS): A Hypothesis for a Common Damage Mechanism of Steatohepatitis |
title_short | Priming, Triggering, Adaptation and Senescence (PTAS): A Hypothesis for a Common Damage Mechanism of Steatohepatitis |
title_sort | priming, triggering, adaptation and senescence (ptas): a hypothesis for a common damage mechanism of steatohepatitis |
topic | Hypothesis |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8624051/ https://www.ncbi.nlm.nih.gov/pubmed/34830427 http://dx.doi.org/10.3390/ijms222212545 |
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