
肝臓のRelAとSTAT3シグナル経路が、一次胆汁酸の合成を促進し、腸管炎症を悪化させる。


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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.

### Competing Interest Statement

The authors have declared no competing interest.

A hepatocyte-specific transcriptional program driven by Rela and Stat3 exacerbates experimental colitis in mice by modulating bile synthesis

肝細胞特異的な転写プログラムがrelaとstat3によって駆動され-マウスの実験的大腸炎を悪化させる-胆汁合成の調節を通して


肝細胞特異的な転写プログラムがRelAとSTAT3によって駆動され、マウスの実験的大腸炎を悪化させる - 胆汁合成の調節を通して
