Localization and function of FGF10 and FGFR2 in the gastric mucosa of rats during postnatal development

• Grant number: 24/13338-4
• Support Opportunities: Scholarships in Brazil - Master
• Start date: July 01, 2025
• End date: August 31, 2026
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Patrícia Gama
• Grantee: Fabiana de Abreu Silva
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The gastric body is the main region of the digestive process and is composed of tubular glands lined by gastric pits. In adult animals, these glands are subdivided into isthmus, neck and base, which contain different epithelial populations responsible for the digestion of food particles through the action of digestive enzymes such as pepsin (zymogenic cells) and acid secretions such as hydrochloric acid (parietal cells), in addition to protecting the gastric mucosa through the production of neutral and acid glycoproteins (mucous cells), promoting the renewal of the epithelium (stem cells) and the secretion of hormones (enteroendocrine cells). The formation of the stomach in mice begins around embryonic day (E) 9.5 and its secondary transition process (cytodifferentiation) occurs between E15.5 and 16.5, which culminates in the presence of rudimentary gastric glands containing their epithelial types. The process of stomach formation during the embryonic period is related to a series of epithelial-mesenchymal signaling molecules, such as fibroblast growth factor 10 (FGF10). This molecule, of mesenchymal origin and paracrine action, binds to its main receptor of epithelial origin, Fgfr2b, which in the presence of the proteoglycan cofactor heparan sulfate (HSPG), is activated forming ternary signaling complexes that activates metabolic pathways related to cell proliferation, migration and differentiation in organs during embryonic development, in adult homeostasis and in pathologies. The maturation of the stomach occurs only during the first three weeks of postnatal life of rats, a period that coincides with breastfeeding, which transfers carbohydrates, lipids, vitamins, minerals, immune and growth factors through the milk that help in the maturation of the organ. During the weaning period, the animals become independent and the gastric glands assume their adult form, enabling the digestion of other foods. However, the role of FGF10 in stomach maturation in the postnatal period is still unknown. Considering its role in the embryogenesis of the stomach and organs such as the intestine and pancreas, as well as in diseases such as breast cancer, and its impacts on cell proliferation, this project aims to evaluate the function of this growth factor in the ontogeny of the gastric body during the first month of life of Wistar rats (Rattus norvegicus). For this purpose, stomach samples from animals aged 3, 7, 14, 18, 21 and 30 days will be collected to evaluate gene expression, morphology and detection of these proteins. The results will be grouped and statistically analyzed.