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The role of signaling pathways in the control of cell proliferation and differentiation of the gastric mucosa

Grant number: 10/17851-5
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): February 01, 2011
Effective date (End): November 30, 2013
Field of knowledge:Biological Sciences - Morphology - Cytology and Cell Biology
Principal researcher:Patrícia Gama
Grantee:Luciana Harumi Osaki
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil


The growth and maturation of the stomach involve the balance between cell proliferation, migration, differentiation and death. These cell processes, in turn, are controlled by the interaction of different elements such as hormones, food, growth factors, milk-borne molecules and genetic program. Early weaning, which means an abrupt change of the feeding pattern, stimulates the proliferation of the gastric epithelium and also increases the protein levels of TGFalpha and its receptor EGFR and changes the localization of TGFbeta3 expression. Additionally, there is an increased activation of Src and MAPK signaling pathways, which can be stimulated by EGFR. Because early weaning induces changes in TGFalpha/EGFR and TGFbeta expression, our aim is to evaluate how exogenous (food) and tissue elements regulate their effects through cell signaling, since there can be an interaction between the signaling pathways stimulated by TGFalpha/EGFR and TGFbeta, which can be essential to the regulation of gastric growth. To that, we will study the interactions between these elements and their effects on gastric cell proliferation in vivo and in vitro by using specific inhibitors for each signaling pathway analyzed. In vivo, early weaning model will be used to evaluate the role of cascades stimulated by TGFalpha/EGFR and TGFbeta in cell proliferation and differentiation of the gastric mucosa. In vitro, epithelial gastric cells will be used to study the crosstalk between the signaling pathways activated by both growth factors and the effects on cell proliferation, also analyzing the levels and expression of cell cycle-related proteins.

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