Priming, Triggering, Adaptation and Senescence (PTAS): A Hypothesis for a Common Damage Mechanism of Steatohepatitis.
Int J Mol Sci
; 22(22)2021 Nov 21.
Article
em En
| MEDLINE
| ID: mdl-34830427
ABSTRACT
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.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Senescência Celular
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Carcinoma Hepatocelular
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Fígado Gorduroso
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Neoplasias Hepáticas
Limite:
Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article