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Canadian Journal of Gastroenterology
Volume 27, Issue 1, Pages e5-e7
http://dx.doi.org/10.1155/2013/676430
Original Article

Hedgehog Signalling is Downregulated in Celiac Disease

Rui Liang,1,2,3 Rupert Hinds,4,5 Helen E Abud,6 and Wei Cheng1,2,3,4,7

1Key Laboratory of Developmental Diseases in Childhood (Chongqing Medical University), Ministry of Education, China
2Department of Paediatric Surgery, Monash Medical Centre, Southern Health, Australia
3Monash Institute of Medical Research, Australia
4Department of Paediatrics, Southern Health, Australia
5Department of Paediatric Gastroenterology, Southern Medical School, Faculty of Medicine, Nursing and Health Sciences, Canada
6Department of Anatomy and Developmental Biology, Monash University, Victoria, Australia
7Department of Surgery, Monash University, Victoria, Australia

Received 14 March 2012; Accepted 12 August 2012

Copyright © 2013 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.