Impact of Global <i>Fxr</i> Deficiency on Experimental Acute Pancreatitis and Genetic Variation in the <i>FXR - Figure 2 </i> Locus in Human Acute Pancreatitis

<p>A - Representative pancreatic histology following induction of acute pancreatitis (H&E staining, 20x and 100x consecutive magnifications for each experimental group): wild-type control (a,b); wild-type acute pancreatitis (c,d); Fxr^-/- control (e,f); Fxr^-/- acute pancreatitis (g,h). B – Semi-quantitative composite pancreatitis severity score of histopathological examination of pancreas samples from wild-type and Fxr^-/- mice with and without acute pancreatitis. Absence of <i>Fxr</i> does not result in more severe acute pancreatitis. C – Ileal mRNA expression of <i>Fgf15</i> in wild-type and Fxr^-/- mice with and without early acute pancreatitis. <i>Fgf15</i> expression was decreased in wild-type mice with acute pancreatitis. Bars indicate mean and SEM.</p

FGF19 plasma levels in patients with predicted severe acute pancreatitis during continuous enteral nutrition.

<p>For comparison, FGF19 plasma levels of healthy controls in the fasting state and after a single bolus of fat are also shown. The postprandial levels represent the average of plasma FGF19 levels at 2, 3, 4 and 6 hours after fat ingestion. There appears to be a blunted FGF19 release in the pancreatitis group. Bars indicate mean and SD.</p

Impact of Global <i>Fxr</i> Deficiency on Experimental Acute Pancreatitis and Genetic Variation in the <i>FXR - Figure 1 </i> Locus in Human Acute Pancreatitis

<p>A – Representative pancreatic histology of wild-type mice from the control group (a, b) and mice with early (c, d) and late (e, f) acute pancreatitis (H&E staining, 20x and 100x magnifications consecutively). Control mice have normal pancreatic morphology, whereas mice of the early pancreatitis group exhibit edema, influx of neutrophils and necrosis. Mice of the late pancreatitis group have no edema or necrosis, but show influx of lymphocytes and fibroblasts. B – Transepithelial electrical resistance of the ileum measured by Ussing chamber experiments. The resistance of the ileum was lower in the early pancreatitis group in comparison to both controls and the late pancreatitis group. C – Ileal mRNA expression of <i>Fxr</i> and FXR target-genes <i>Asbt</i>, <i>Shp</i>, <i>Fgf15</i>, and <i>Ibabp</i>, and <i>Villin</i> in wild-type mice of the control group, and the early and late pancreatitis groups. Expression of <i>Fxr</i>, <i>Asbt</i> and <i>Villin</i> did not differ between experimental groups. Expression of the other Fxr target genes was lower in early acute pancreatitis, but not in late pancreatitis. D – Ileal mRNA expression of genes implicated in intestinal barrier function, <i>iNos</i>, <i>Ang1</i>, <i>Car12</i>, <i>IL18</i>. Expression of <i>Ang1</i> was lowered in the early pancreatitis group, the other genes remained similar in the different experimental conditions. E – Hepatic expression of <i>Fxr</i>, <i>Shp</i>, <i>iNos</i> and <i>Ang1</i>. Hepatic <i>Ang1</i> was increased in early pancreatitis, whereas the expression of the other genes was lowered in the early acute pancreatitis group. Expression levels were normalized to cyclophilin expression. Bars indicate means and SEM, * p<0.05, ** p<0.01, *** p<0.001.</p