Hedgehog signalling is downregulated in celiac disease

Abstract

BACKGROUND: Celiac disease (CD) is a common autoimmune disorder of the small intestine that occurs in genetically predisposed individuals. Animal studies have suggested that the hedgehog (Hh) signalling pathway is involved in gut inflammation, injury and repair. OBJECTIVE: To examine the expression of components of the Hh signalling pathway in CD. METHODS: Children undergoing gastroscopy investigation for CD at Monash University (Victoria, Australia), and other children undergoing gastroscopy in whom small bowel pathology was not expected (ie, controls), were included in the present study. One histopathologist, who was blinded to the biopsy data, analyzed the biopsies and a diagnosis of CD was made according to standard Marsh criteria. From these samples, RNA was extracted and complementary DNA was synthesized using reverse transcription polymerase chain reaction. The levels of Hh ligand Sonic hh, Indian hh, protein patched homologue 1 (PTCH 1) and bone morphogenetic protein 4 (BMP4) messenger RNA were quantified by real-time polymerase chain reaction. Relative expression quantification was performed using the ΔΔCt method. RESULTS: Duodenal biopsies were collected from 37 children. There were 20 CD specimens and 17 normal controls. The relative expression of Sonic hh from CD patients was 58% lower than that of the controls; similarly, Indian hh expression was decreased in children with CD by 44%. Compared with controls, the expression of Hh receptor PTCH 1 decreased by 71% and the expression of the Hh target gene BMP4 by 42%. CONCLUSIONS: The expression of the Hh signalling pathway genes was consistently downregulated in untreated CD children. These results suggest that the Hh signalling pathway plays a role in the mucosal lesions encountered in CD. ©2013 Pulsus Group Inc. All rights reserved.