SYNDICATED ARTICLE

Reprinted with Permission from Gut

Sonic hedgehog expression correlates with fundic gland differentiation in the adult gastrointestinal tract

G R van den Brink¹, J C H Hardwick¹, C Nielsen², C Xu¹, F J ten Kate³, J Glickman⁴, S J H van Deventer⁵, D J Roberts², M P Peppelenbosch¹

¹ Department of Experimental Internal Medicine, Academic Medical Centre, Amsterdam, the Netherlands
² Department of Pediatric Surgery, Massachusetts General Hospital, Brigham and Women’s Hospital, Boston, USA
³ Department of Pathology, Academic Medical Centre, Amsterdam, the Netherlands
⁴ Department of Pathology, Brigham and Women’s Hospital, Boston, USA
⁵ Department of Gastroenterology, Academic Medical Centre, Amsterdam, the Netherlands

Correspondence to:
Correspondence to:
G van den Brink, Lab Exp Internal Medicine, Room G2-130, Academic Medical Centre, Meibergdreef 9, 1105 AZ, Amsterdam, the Netherlands;
g.r.vandenbrink{at}amc.uva.nl

Background: Sonic hedgehog (Shh) is an important endodermal morphogenetic signal during the development of the vertebrate gut. It controls gastrointestinal patterning in general, and gastric gland formation in particular. We have previously shown that Shh regulates gastric gland proliferation in the adult but detailed analysis of its expression along the adult gastrointestinal tract has never been undertaken. We therefore studied Shh expression along the normal human and rodent adult gastrointestinal tract as well as in intestinal metaplasia of the stomach, gastric and intestinal metaplasia of the oesophagus, and gastric heterotopia in Meckel’s diverticulum.

Methods: The studies were performed with in situ hybridisation and by immunohistochemistry using an antibody that recognises the Shh precursor form.

Results: We found that in the normal gastrointestinal tract, high levels of Shh were expressed in the fundic glands of the stomach. Shh expression was also found in fundic gland metaplasia and heterotopia. However, Shh expression was lost in intestinal metaplasia of the stomach.

Conclusion: We found a strong correlation between Shh expression and fundic gland differentiation. Our current study therefore provides evidence that in addition to its role in gastric epithelial development, Shh plays a unique role in gastric epithelial differentiation in adults.

Keywords: sonic hedgehog; fundic gland; fundic gland differentiation

Abbreviations: Hh, hedgehog; Shh, sonic hedgehog; MUC, mucin; PBS, phosphate buffered saline; strep ß-gal, streptavidin ß-galactosidase; HHG, hyperplastic hypersecretory gastropathy

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