Increased expression of hypoxia-inducible factor 1alpha 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-1alpha 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-1alpha, trefoil factor 1 (TFF1), ecto-5-prime nucleotidase (CD73), and multi drug resistance gene 1 (MDR1) mRNA and HIF-1alpha protein expression were determined by real-time PCR and Western blot, respectively. Localization of HIF-1alpha was determined by immunofluorescent staining. We found increased HIF-1alpha and TFF1 mRNA and HIF-1alpha 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-1alpha 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-1alpha expression in CD children suggest the contribution of this signaling pathway in the pathomechanism of CD.
Vannay
Adám
A
First Department of Pediatrics, Semmelweis University, H-1083 Budapest, Hungary.
Sziksz
Erna
E
Prókai
Agnes
A
Veres
Gábor
G
Molnár
Kriszta
K
Szakál
Dorottya Nagy
DN
Onódy
Anna
A
Korponay-Szabó
Ilma R
IR
Szabó
András
A
Tulassay
Tivadar
T
Arató
András
A
Szebeni
Beáta
B
D015720:5'-Nucleotidase / Q000235:genetics / Q000378:metabolism; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism; D000293:Adolescent; D001706:Biopsy; D002446:Celiac Disease / Q000378:metabolism* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D004386:Duodenum / Q000166:cytology / Q000378:metabolism / Q000601:surgery; D005260:Female; D058851:GPI-Linked Proteins; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D000071163:Trefoil Factor-1; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D058851:GPI-Linked Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012333:RNA, Messenger; C051838:TFF1 protein, human; D000071163:Trefoil Factor-1; D025521:Tumor Suppressor Proteins; D015720:5'-Nucleotidase; C548241:NT5E protein, human