Document Detail


Spasmolytic polypeptide-expressing metaplasia (SPEM) in the gastric oxyntic mucosa does not arise from Lgr5-expressing cells.
MedLine Citation:
PMID:  22198711     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: Metaplastic lineages in the oxyntic mucosa of the stomach are critical preneoplastic precursors of gastric cancer. Recent studies have demonstrated that spasmolytic polypeptide-expressing metaplasia (SPEM) in the mouse oxyntic mucosa arises from transdifferentiation of mature gastric chief cells. Other investigations of intestinal progenitor cells have shown that cells demonstrating transcriptional activity for leucine-rich repeat containing G-protein-coupled receptor 5 (Lgr5) in the intestine, colon and gastric antrum function as adult stem cells. We have now investigated whether cells demonstrating Lgr5 transcriptional activity in the oxyntic mucosa of mice might be responsible for development of metaplasia.
DESIGN: Lgr5-EGFP-IRES-Cre(ERT2/+);Rosa26R mice were used to examine the distribution of Lgr5 transcriptionally active cells in the normal oxyntic mucosa as well as after treatment with DMP-777 or L-635 to induce acute SPEM. Lineage mapping was performed to determine if Lgr5-expressing cells gave rise to SPEM.
RESULTS: Cells expressing transcriptional activity for Lgr5 in the oxyntic mucosa were present as scattered rare cells only along the lesser curvature of the stomach. These cells also stained for markers of chief cells (intrinsic factor and pepsinogen) but never showed any staining for proliferative markers (Ki-67). In Lgr5-EGFP-IRES-Cre(ERT2/+);Rosa26R mice induced with tamoxifen, treatment with either DMP-777 or L-635 to induce acute oxyntic atrophy caused induction of SPEM, but no lineage mapping into SPEM from Lgr5-expressing cells was observed.
CONCLUSION: The results indicate that, while chief cells with Lgr5 transcriptional activity are present along the lesser curvature of the gastric oxyntic mucosa, they are not responsible for production of metaplasia.
Authors:
Ki Taek Nam; Ryan L O'Neal; Robert J Coffey; Paul E Finke; Nick Barker; James R Goldenring
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2011-12-23
Journal Detail:
Title:  Gut     Volume:  61     ISSN:  1468-3288     ISO Abbreviation:  Gut     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-11-12     Completed Date:  2013-01-14     Revised Date:  2013-09-16    
Medline Journal Info:
Nlm Unique ID:  2985108R     Medline TA:  Gut     Country:  England    
Other Details:
Languages:  eng     Pagination:  1678-85     Citation Subset:  AIM; IM    
Affiliation:
Nashville VA Medical Center and the Department of Surgery, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2733, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Azetidines
Biological Markers / metabolism
Cell Lineage
Immunohistochemistry
Metaplasia
Mice
Parietal Cells, Gastric / metabolism,  pathology*
Peptides / metabolism*
Piperazines
Precancerous Conditions / chemically induced,  metabolism,  pathology*
Receptors, G-Protein-Coupled / metabolism*
Stomach Neoplasms / chemically induced,  metabolism,  pathology*
Tumor Markers, Biological / metabolism*
beta-Galactosidase / metabolism
Grant Support
ID/Acronym/Agency:
P30 DK058404/DK/NIDDK NIH HHS; R01 DK071590/DK/NIDDK NIH HHS; R01 DK071590/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Azetidines; 0/Biological Markers; 0/DMP 777; 0/Lgr5 protein, mouse; 0/Peptides; 0/Piperazines; 0/Receptors, G-Protein-Coupled; 0/Tumor Markers, Biological; 0/spasmolytic polypeptide; EC 3.2.1.23/beta-Galactosidase
Comments/Corrections
Comment In:
Gut. 2012 Dec;61(12):1777-8   [PMID:  22442165 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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