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EXPRESSION PATTERNS OF THE HEDGEHOG PROTEIN FAMILY IN DEVELOPING HUMAN GASTRIC GLAND
S Turgeon, VWT Émond, D Ménard, N Perreault
Équipe IRSC sur l’épithélium digestif Département d’Anatomie et de Biologie Cellulaire, FMSS, Université de Sherbrooke
BACKGROUND: Hedgehogs (Hh) are morphogenes known to regulate numerous cell processes in various tissues. In the gastrointestinal tract, Sonic (Shh) and Indian (Ihh) hedgehog proteins have been shown to play roles in morphogenesis, cancer and the inflammatory diseases. Recent studies with mouse models have reported an important role for Ihh and Shh in stem cell homeostasis, proliferation and maintenance of vertical axis architecture. However, the expression pattern of these proteins in the development of the human gastric gland has not yet been explored.
AIM: To analyze variations in the expression patterns of Hh protein members as well as their target genes in the early stages of human gastric development.
METHODS AND RESULTS: With foetal human stomach tissues ranging from 14 to 20 weeks of gestation, we have studied the variation in the expression pattern of various proteins from the Hh signaling pathway in human gastric development. The profile of expression of Ihh revealed a dramatic increase between 14 and 17 weeks as shown by immunostaining and western blot analysis. Moreover, Ihh immunolocalization showed the protein to be expressed in epithelial cells at the surface of the gland. Immunostaining for Shh showed a constant increase of expression between 14 and 20 weeks of gestation. Shh protein localization was found throughout the gland. Immunostaining for Hh target genes such as Bmp2 and Bmp4 exposed the same strong increase between 14 and 17 weeks seen with the Ihh protein.
CONCLUSION: Altogether, these results suggest that proteins from the Hh signaling pathway play a role in the development and establishment of the gastric pit-gland axis. Knowledge of the normal expression of these molecules during development could lead to a better understanding of their deregulation during numerous gastric pathologies.