Fibroblast Growth Factor 10-Fibroblast Growth Factor Receptor 2b Mediated Signaling Is Not Required for Adult Glandular Stomach Homeostasis

作者: Allison L. Speer , Denise Al Alam , Frederic G. Sala , Henri R. Ford , Saverio Bellusci

DOI: 10.1371/JOURNAL.PONE.0049127

关键词:

摘要: The signaling pathways that are essential for gastric organogenesis have been studied in some detail; however, those regulate the maintenance of epithelium during adult homeostasis remain unclear. In this study, we investigated role Fibroblast growth factor 10 (FGF10) and its main receptor, receptor 2b (FGFR2b), glandular stomach homeostasis. We first showed mouse expressed Fgf10, receptors, Fgfr1b Fgfr2b, most other FGFR2b ligands (Fgf1, Fgf7, Fgf22) except Fgf3 Fgf20. Fgf10 expression was mesenchymal whereas FGFR1 FGFR2 were mostly epithelial. Studying double transgenic mice allow inducible overexpression mice, normal increased epithelial proliferation, drove mucous neck cell differentiation, reduced parietal chief differentiation. Although a similar phenotype can be associated with development metaplasia, found short duration does not cause metaplasia. Finally, investigating soluble form FGF10's which acts as dominant negative, no significant changes proliferation or differentiation mutants. Our work provides evidence, time, FGF10-FGFR2b pathway is required

参考文章(54)
Jovanny Zabaleta, Multifactorial etiology of gastric cancer. Methods of Molecular Biology. ,vol. 863, pp. 411- 435 ,(2012) , 10.1007/978-1-61779-612-8_26
A.J. Mouland, S. Bevan, J.H. White, G.N. Hendy, Human chromogranin A gene. Molecular cloning, structural analysis, and neuroendocrine cell-specific expression. Journal of Biological Chemistry. ,vol. 269, pp. 6918- 6926 ,(1994) , 10.1016/S0021-9258(17)37462-8
James R. Goldenring, Ki Taek Nam, Oxyntic atrophy, metaplasia, and gastric cancer Progress in Molecular Biology and Translational Science. ,vol. 96, pp. 117- 131 ,(2010) , 10.1016/B978-0-12-381280-3.00005-1
Alpers Dh, Gordon M, Misra Dn, Howard Ta, Grove M, Becich Mj, Shao Js, Human gastric intrinsic factor expression is not restricted to parietal cells. Journal of Anatomy. ,vol. 189, pp. 303- 313 ,(1996)
Wallace L. McKeehan, Fen Wang, Mikio Kan, The Heparan Sulfate–Fibroblast Growth Factor Family: Diversity of Structure and Function Progress in Nucleic Acid Research and Molecular Biology. ,vol. 59, pp. 135- 176 ,(1997) , 10.1016/S0079-6603(08)61031-4
M Hajihosseini, B Spencer-Dene, C Dickson, L De Moerlooze, I Rosewell, J M Revest, An important role for the IIIb isoform of fibroblast growth factor receptor 2 (FGFR2) in mesenchymal-epithelial signalling during mouse organogenesis Development. ,vol. 127, pp. 483- 492 ,(2000) , 10.1242/DEV.127.3.483
Frieder Schwenk, Udo Baron, Klaus Rajewsky, A cre-transgenic mouse strain for the ubiquitous deletion of loxP-flanked gene segments including deletion in germ cells. Nucleic Acids Research. ,vol. 23, pp. 5080- 5081 ,(1995) , 10.1093/NAR/23.24.5080
Masahiro Shin, Sumihare Noji, Annette Neubüser, Sadao Yasugi, FGF10 is required for cell proliferation and gland formation in the stomach epithelium of the chicken embryo Developmental Biology. ,vol. 294, pp. 11- 23 ,(2006) , 10.1016/J.YDBIO.2005.12.019
Sara Parsa, Suresh K. Ramasamy, Stijn De Langhe, Varsha V. Gupte, Jody J. Haigh, Daniel Medina, Savério Bellusci, Terminal end bud maintenance in mammary gland is dependent upon FGFR2b signaling Developmental Biology. ,vol. 317, pp. 121- 131 ,(2008) , 10.1016/J.YDBIO.2008.02.014
Gusztav Belteki, Jody Haigh, Nikolett Kabacs, Katharina Haigh, Karen Sison, Frank Costantini, Jeff Whitsett, Susan E Quaggin, Andras Nagy, Conditional and inducible transgene expression in mice through the combinatorial use of Cre-mediated recombination and tetracycline induction Nucleic Acids Research. ,vol. 33, pp. 2765- 2765 ,(2005) , 10.1093/NAR/GNI051