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1: Diabetes. 2007 Jan;56(1):96-106.

FGFR3 is a negative regulator of the expansion of pancreatic epithelial cells.

Arnaud-Dabernat S, Kritzik M, Kayali AG, Zhang YQ, Liu G, Ungles C, Sarvetnick N.

The Scripps Research Institute, Department of Immunology, IMM23, 10550 North
Torrey Pines Rd., La Jolla, CA 92037, USA.

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.

PMID: 17192470 [PubMed - indexed for MEDLINE]

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