Document Detail


FGFR3 is a negative regulator of the expansion of pancreatic epithelial cells.
MedLine Citation:
PMID:  17192470     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Fibroblast growth factors (FGFs) and their receptors (FGFRs) are key signaling molecules for pancreas development. Although FGFR3 is a crucial developmental gene, acting as a negative regulator of bone formation, its participation remains unexplored in pancreatic organogenesis. We found that FGFR3 was expressed in the epithelia in both mouse embryonic and adult regenerating pancreata but was absent in normal adult islets. In FGFR3 knockout mice, we observed an increase in the proliferation of epithelial cells in neonates, leading to a marked increase in islet areas in adults. In vitro studies showed that FGF9 is a very potent ligand for FGFR3 and activates extracellular signal-related kinases (ERKs) in pancreatic cell lines. Moreover, FGFR3 blockade or FGFR3 deficiency led to increased proliferation of pancreatic epithelial cells in vivo. This was accompanied by an increase in the proportion of potential islet progenitor cells. Thus, our results show that FGFR3 signaling inhibits the expansion of the immature pancreatic epithelium. Consequently, this study suggests that FGFR3 participates in regulating pancreatic growth during the emergence of mature islet cells.
Authors:
Sandrine Arnaud-Dabernat; Marcie Kritzik; Ayse G Kayali; You-Qing Zhang; Guoxun Liu; Cory Ungles; Nora Sarvetnick
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Diabetes     Volume:  56     ISSN:  0012-1797     ISO Abbreviation:  Diabetes     Publication Date:  2007 Jan 
Date Detail:
Created Date:  2006-12-28     Completed Date:  2007-03-26     Revised Date:  2012-06-05    
Medline Journal Info:
Nlm Unique ID:  0372763     Medline TA:  Diabetes     Country:  United States    
Other Details:
Languages:  eng     Pagination:  96-106     Citation Subset:  AIM; IM    
Affiliation:
The Scripps Research Institute, Department of Immunology, IMM23, 10550 North Torrey Pines Rd., La Jolla, CA 92037, USA.
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MeSH Terms
Descriptor/Qualifier:
Aging
Animals
Animals, Newborn
Cell Line
Epithelial Cells / cytology*,  drug effects
Islets of Langerhans / cytology,  physiology*
Mice
Mice, Inbred NOD
Mice, Knockout
Pancreas / cytology*,  embryology
Receptor, Fibroblast Growth Factor, Type 3 / deficiency,  genetics,  physiology*
Regeneration
Signal Transduction / physiology
Grant Support
ID/Acronym/Agency:
DK060746-02/DK/NIDDK NIH HHS; T32HL0795/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
EC 2.7.10.1/Fgfr3 protein, mouse; EC 2.7.10.1/Receptor, Fibroblast Growth Factor, Type 3

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


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