title: 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.
authors: Key Laboratory of Developmental Diseases in Childhoold (Chongqing Medical University), Ministry of Education, China.
authors: Rui
authors: R
authors: Liang
authors: Rupert
authors: R
authors: Hinds
authors: Helen E
authors: HE
authors: Abud
authors: Wei
authors: W
authors: Cheng
mesh_terms: D000293:Adolescent; D016022:Case-Control Studies; D002446:Celiac Disease / Q000503:physiopathology*; D002648:Child; D002675:Child, Preschool; D015536:Down-Regulation; D005773:Gastroscopy; D053823:Hedgehog Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000473:pathology*; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics*; D014739:Victoria
chemical_list: D053823:Hedgehog Proteins; D012333:RNA, Messenger
references: Mol Med Today. 1998 Aug;4(8):343-9
references: 9755453
references: Circulation. 2006 May 23;113(20):2413-24
references: 16702471
references: Nat Med. 2005 Nov;11(11):1197-204
references: 16244652
references: Nature. 2004 Nov 18;432(7015):324-31
references: 15549094
references: Gastroenterology. 2010 Jun;138(7):2368-77, 2377.e1-4
references: 20206176
references: Gastroenterology. 2010 Sep;139(3):893-903
references: 20542037
references: Development. 2005 Jan;132(2):279-89
references: 15590741
references: J Cell Mol Med. 2009 Aug;13(8B):2424-2435
references: 18662193
references: Histochem Cell Biol. 2003 Mar;119(3):233-7
references: 12649738
references: Nature. 2007 Oct 25;449(7165):1003-7
references: 17934449
references: Development. 2010 May;137(10):1721-9
references: 20430747
references: Development. 2000 May;127(9):1971-80
references: 10751185
references: Development. 2000 Jun;127(12):2763-72
references: 10821773
references: Nature. 2011 Apr 7;472(7341):110-4
references: 21389986
references: Lab Invest. 2004 Dec;84(12):1631-42
references: 15502857
references: Gastroenterology. 2010 Nov;139(5):1665-76, 1676.e1-10
references: 20682322
references: J Gastroenterol. 2009;44(5):372-9
references: 19291354
references: PLoS Med. 2008 Dec 9;5(12):e239
references: 19071955