A hepatocyte-specific transcriptional program driven by Rela and Stat3 exacerbates experimental colitis in mice by modulating bile synthesis.
Elife
; 122024 Aug 13.
Article
en En
| MEDLINE
| ID: mdl-39137024
ABSTRACT
Hepatic factors secreted by the liver promote homeostasis and are pivotal for maintaining the liver-gut axis. Bile acid metabolism is one such example wherein, bile acid synthesis occurs in the liver and its biotransformation happens in the intestine. Dysfunctional interactions between the liver and the intestine stimulate varied pathological outcomes through its bidirectional portal communication. Indeed, aberrant bile acid metabolism has been reported in inflammatory bowel disease (IBD). However, the molecular mechanisms underlying these crosstalks that perpetuate intestinal permeability and inflammation remain obscure. Here, we identify a novel hepatic gene program regulated by Rela and Stat3 that accentuates the inflammation in an acute experimental colitis model. Hepatocyte-specific ablation of Rela and Stat3 reduces the levels of primary bile acids in both the liver and the gut and shows a restricted colitogenic phenotype. On supplementation of chenodeoxycholic acid (CDCA), knock-out mice exhibit enhanced colitis-induced alterations. This study provides persuasive evidence for the development of multi-organ strategies for treating IBD and identifies a hepatocyte-specific Rela-Stat3 network as a promising therapeutic target.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Ácidos y Sales Biliares
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Colitis
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Ratones Noqueados
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Hepatocitos
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Modelos Animales de Enfermedad
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Factor de Transcripción STAT3
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Factor de Transcripción ReIA
Límite:
Animals
Idioma:
En
Revista:
Elife
Año:
2024
Tipo del documento:
Article
País de afiliación:
India
Pais de publicación:
Reino Unido