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Loss of Sonic Hedgehog in the adult stomach results in foveolar hyperplasia and delayed differentiation of the zymogenic cell lineage
Author(s) -
Xiao Chang,
Roland Joseph,
Nam Ki Taek,
Goldenring James R,
Zavros Yana
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.1007.10
Subject(s) - foveolar cell , biology , sonic hedgehog , hedgehog , cellular differentiation , parietal cell , epithelium , gastric glands , microbiology and biotechnology , gastric mucosa , pathology , endocrinology , stomach , cancer research , medicine , signal transduction , biochemistry , genetics , gene
Objective Parietal cell‐expressed Sonic Hedgehog (Shh) regulates function and differentiation of the gastric epithelium. Correlative evidence shows that loss of Shh expression associated with Helicobacter pylori infection results in the disruption of the normal gastric epithelium. We sought to identify whether Shh regulates gastric epithelial cell differentiation in the absence of inflammation. Methods A parietal cell‐specific, tamoxifen‐inducible deletion of Shh mouse model was developed (HKCre Ind /Shh KO ). Epithelial cell proliferation and migration was studied using BrdU and Ki67 co‐immunostaining. Cell lineage changes were studied using markers specific for surface mucous (Ulex europaeus, UEAI), mucous neck (Griffonia simplicifolia, GSII) and zymogen (intrinsic factor, IF) cells. Results Compared to Controls, HKCre Ind /Shh KO mice developed foveolar hyperplasia reflected by an expansion of BrdU/UEAI positive cells. HKCre Ind /Shh KO mice also showed an expansion of GSII/IF co‐expressing cells at the base of the gastric gland. Co‐localization of BrdU and Ki67 revealed loss of normal migration of the epithelial cells within HKCre Ind /Shh KO mouse stomachs. Conclusion Loss of Shh in the adult stomach results in the development of foveolar hyperplasia and delayed differentiation of the zymogenic cell lineage independent of inflammation. (DHC Pilot and Feasibility Project Award, Zavros)