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...

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Autores principales:	Peter M. Abuja, Kurt Zatloukal, Helmut Denk
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	steatohepatitis pathomechanism metabolism stress defence mitochondrial damage hypoxic signalling Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/9450e15faeb3425791911561c435697c
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spelling	oai:doaj.org-article:9450e15faeb3425791911561c435697c2021-11-25T17:57:40ZPriming, Triggering, Adaptation and Senescence (PTAS): A Hypothesis for a Common Damage Mechanism of Steatohepatitis10.3390/ijms2222125451422-00671661-6596https://doaj.org/article/9450e15faeb3425791911561c435697c2021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12545https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Understanding 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.Peter M. AbujaKurt ZatloukalHelmut DenkMDPI AGarticlesteatohepatitispathomechanismmetabolismstress defencemitochondrial damagehypoxic signallingBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12545, p 12545 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	steatohepatitis pathomechanism metabolism stress defence mitochondrial damage hypoxic signalling Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	steatohepatitis pathomechanism metabolism stress defence mitochondrial damage hypoxic signalling Biology (General) QH301-705.5 Chemistry QD1-999 Peter M. Abuja Kurt Zatloukal Helmut Denk Priming, Triggering, Adaptation and Senescence (PTAS): A Hypothesis for a Common Damage Mechanism of Steatohepatitis
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	article
author	Peter M. Abuja Kurt Zatloukal Helmut Denk
author_facet	Peter M. Abuja Kurt Zatloukal Helmut Denk
author_sort	Peter M. Abuja
title	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_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_sort	priming, triggering, adaptation and senescence (ptas): a hypothesis for a common damage mechanism of steatohepatitis
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/9450e15faeb3425791911561c435697c
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Priming, Triggering, Adaptation and Senescence (PTAS): A Hypothesis for a Common Damage Mechanism of Steatohepatitis

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