Increased Expression of Hypoxia-Inducible Factor 1α in Coeliac Disease

Previously, it has been suggested that hypoxia-inducible factor (HIF) 1 signaling may play determinative role in the maintenance of the barrier function of the intestinal epithelium in inflammatory bowel disease. Our aim was to depict the alteration of HIF-1 alpha and related genes in celiac disease (CD) where the importance of the barrier function is well known. Duodenal biopsy specimens were collected from 16 children with untreated CD, 9 children with treated CD and 10 controls. HIF-1 alpha, trefoil factor 1 (TFF1), ecto-5-prime nucleotidase (CD73), and multi drug resistance gene 1 (MDR1) mRNA and HIF-1 alpha protein expression were determined by real-time PCR and Western blot, respectively. Localization of HIF-1 alpha was determined by immunofluorescent staining. We found increased HIF-1 alpha and TFF1 mRNA and HIF-1 alpha protein expression in the duodenal mucosa of children with untreated CD compared with controls or children with treated CD (p < 0.05). In untreated CD children, HIF-1 alpha staining was present in cytoplasmic and nuclear region of the villous enterocytes. In treated CD mRNA expression of CD73 and MDR1 were increased compared with controls (p < 0.01 and 0.05. respectively). Our results of increased mucosal HIF-1 alpha expression in CD children suggest the contribution of this signaling pathway in the pathomechanism of CD. (Pediatr Res 68: 118-122, 2010)