《Table 2 Effects of experimental perturbations of hepatocyte nuclear factor 4alpha》

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《Role of hepatocyte nuclear factor 4-alpha in gastrointestinal and liver diseases》

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Intestine targeted knockout of HNF4αin mice increased susceptibility to dextran sulfate sodium（DSS）induced colitis[1，56].In another study，knockout of P1 and P2isoforms of HNF4αin mice resulted in spontaneous intestinal inflammation that worsened with time，leading to epithelial injury，crypt hyperplasia，and proliferation[57].HNF4αderived from P1 or P2 promoters have distinct effects on colonic epithelium，as demonstrated with an exon swapping mouse model[2].Mice expressing only P1 promoter-derivedα1 isoform HNF4αdeveloped fewer and smaller tumors than wild type mice after treatment with DSS and azoxymethane（AOM），and lesssusceptibility to DSS-induced colitis.In contrast，expression of only P2 promoterderivedα7 isoform HNF4αresulted in greater tumor load and number than wild type mice and were highly sensitive to DSS-induced colitis[2].HNF4αdirectly modulated expression of Na+/H+exchanger isoform 3（NHE3），which has been implicated in IBDpathogenesis[58].