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• W2912942295 abstract "Abstract Background & Aims Loss of hepatocyte nuclear factor‐4α ( HNF 4α), a critical factor driving liver development and differentiation, is frequently associated with hepatocellular carcinoma ( HCC ). Our recent data revealed that HNF 4α level was decreased in mouse and human HCC s with activated β‐catenin signalling. In addition, increasing HNF 4α level by miR‐34a inhibition slowed tumour progression of β‐catenin‐activated HCC in mice. Methods We generated a Hnf4a flox/flox/ Apc flox/flox / TTR ‐Cre ERT 2 ( Hnf4a/Apc ∆Hep ) mouse line and evaluated the impact of Hnf4a disruption on HCC development and liver homoeostasis. Results There was no significant impact of Hnf4a disruption on tumour onset and progression in Apc ∆Hep model. However, we observed an unexpected phenotype in 28% of Hnf4a ∆Hep mice maintained in a conventional animal facility, which presented disorganized portal triads, characterized by stenosis of the portal vein and increased number and size of hepatic arteries and bile ducts. These abnormal portal structures resemble the human idiopathic non‐cirrhotic portal hypertension syndrome. We correlated the presence of portal remodelling with a higher expression of protein and mRNA levels of TGF β and BMP 7, a key regulator of the TGF β‐dependent endothelial‐to‐mesenchymal transition. Conclusion These data demonstrate that HNF 4α does not play a major role during β‐catenin‐driven HCC , thus revealing that the tumour suppressor role of HNF 4α is far more complex and dependent probably on its temporal expression and tumour context. However, HNF 4α loss in adult hepatocytes could induce abnormal portal structures resembling the human idiopathic non‐cirrhotic portal hypertension syndrome, which may result from endothelial‐ and epithelial‐to‐mesenchymal transitions." @default.
• W2912942295 created "2019-02-21" @default.
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• W2912942295 date "2019-02-24" @default.
• W2912942295 modified "2023-10-16" @default.
• W2912942295 title "The concomitant loss of <scp>APC</scp> and <scp>HNF</scp> 4α in adult hepatocytes does not contribute to hepatocarcinogenesis driven by β‐catenin activation" @default.
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• W2912942295 doi "https://doi.org/10.1111/liv.14068" @default.
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