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Hedgehog signalling stimulates precursor cell accumulation and impairs epithelial maturation in the murine oesophagus.
MedLine Citation:
PMID:  22504664     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
ObjectiveIn the intestine Hedgehog (Hh) signalling is directed from epithelium to mesenchyme and negatively regulates epithelial precursor cell fate. The role of Hh signalling in the oesophagus has not been studied in vivo. Here the authors examined the role of Hh signalling in epithelial homeostasis of oesophagus.DesignThe authors used transgenic mice in which the Hh receptor Patched1 (Ptch1) could be conditionally inactivated in a body-wide manner and mice in which Gli1 could be induced specifically in the epithelium of the skin and oesophagus. Effects on epithelial homeostasis of the oesophagus were examined using immunohistochemistry, in situ hybridisation, transmission electron microscopy and real-time PCR. Hh signalling was examined in patients with oesophageal squamous cell carcinoma (SCC) by quantitative real-time PCR.ResultsSonic Hh is signalled in an autocrine manner in the basal layer of the oesophagus. Activation of Hh signalling resulted in an expansion of the epithelial precursor cell compartment and failure of epithelial maturation and migration. Levels of Hh targets GLI1, HHIP and PTCH1 were increased in SCC compared with normal tissue from the same patients.ConclusionHere the authors find that Hh signalling positively regulates the precursor cell compartment in the oesophageal epithelium in an autocrine manner. Since Hh signalling targets precursor cells in the oesophageal epithelium and signalling is increased in SCCs, Hh signalling may be involved in oesophageal SCC formation.
Authors:
Willemijn A van Dop; Sanne L Rosekrans; Anja Uhmann; Viljar Jaks; G Johan A Offerhaus; Marius A van den Bergh Weerman; Maria Kasper; Jarom Heijmans; James C H Hardwick; Hein W Verspaget; Daan W Hommes; Rune Toftgård; Heidi Hahn; Gijs R van den Brink
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-4-13
Journal Detail:
Title:  Gut     Volume:  -     ISSN:  1468-3288     ISO Abbreviation:  -     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-4-16     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2985108R     Medline TA:  Gut     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Academic Medical Center, Amsterdam, The Netherlands.
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