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

Sandrine Arnaud-Dabernat, Marcie Kritzik, Ayse G. Kayali, You Qing Zhang, Guoxun Liu, Cory Ungles, Nora Sarvetnick

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)96-106
Number of pages11
JournalDiabetes
Volume56
Issue number1
DOIs
StatePublished - Jan 1 2007

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Islets of Langerhans
Pancreas
Epithelium
Epithelial Cells
Developmental Genes
Fibroblast Growth Factor Receptors
Organogenesis
Osteogenesis
Knockout Mice
Phosphotransferases
Stem Cells
Ligands
Cell Line
Growth
In Vitro Techniques

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Arnaud-Dabernat, S., Kritzik, M., Kayali, A. G., Zhang, Y. Q., Liu, G., Ungles, C., & Sarvetnick, N. (2007). FGFR3 is a negative regulator of the expansion of pancreatic epithelial cells. Diabetes, 56(1), 96-106. https://doi.org/10.2337/db05-1073

FGFR3 is a negative regulator of the expansion of pancreatic epithelial cells. / Arnaud-Dabernat, Sandrine; Kritzik, Marcie; Kayali, Ayse G.; Zhang, You Qing; Liu, Guoxun; Ungles, Cory; Sarvetnick, Nora.

In: Diabetes, Vol. 56, No. 1, 01.01.2007, p. 96-106.

Research output: Contribution to journalArticle

Arnaud-Dabernat, S, Kritzik, M, Kayali, AG, Zhang, YQ, Liu, G, Ungles, C & Sarvetnick, N 2007, 'FGFR3 is a negative regulator of the expansion of pancreatic epithelial cells', Diabetes, vol. 56, no. 1, pp. 96-106. https://doi.org/10.2337/db05-1073
Arnaud-Dabernat S, Kritzik M, Kayali AG, Zhang YQ, Liu G, Ungles C et al. FGFR3 is a negative regulator of the expansion of pancreatic epithelial cells. Diabetes. 2007 Jan 1;56(1):96-106. https://doi.org/10.2337/db05-1073
Arnaud-Dabernat, Sandrine ; Kritzik, Marcie ; Kayali, Ayse G. ; Zhang, You Qing ; Liu, Guoxun ; Ungles, Cory ; Sarvetnick, Nora. / FGFR3 is a negative regulator of the expansion of pancreatic epithelial cells. In: Diabetes. 2007 ; Vol. 56, No. 1. pp. 96-106.
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