Characterization of cell proliferation behavior in the rat gastric mucosa: immediate and late effects of early weaning

• Grant number: 20/05117-7
• Support Opportunities: Regular Research Grants
• Start date: November 01, 2021
• End date: January 31, 2024
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Patrícia Gama
• Grantee: Patrícia Gama
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Israel Tojal da Silva
• Associated scholarship(s): 22/03473-6 - Proliferation and differentiation in the gastric mucosa: the investigation of target genes, BP.TT

Abstract

The gastric mucosa in the corpus area is constituted of tubular glands that open to the surface through pits, and in these glands three regions are identified: isthmus, neck and base. Proliferative cells are concentrated between the isthmus and the neck of the gland, but the gland base presents a secondary niche for zymogenic cells cycle. During postnatal development, the proliferative niches are not established, making proliferative cells spread along the gland. It is known that the interaction between epithelium and connective tissue is essential for molecular communication, and the myofibroblasts produce regulatory molecules for proliferative niches that can affect the localization and activity of stem and progenitor cells. Though many studies are under way and being constantly debated, still there is no marker for gastric stem cells. During postnatal development, early weaning alters cell proliferation and moves cycling cells towards the isthmus, but the elements that determine such movement, and how cells are molecularly influenced by feeding pattern remain unknown. Our aim is to evaluate the elements that establish gradients for proliferative niches and determine proliferation and migration in pups and adult animals, and also to identify early and late effects in stem and progenitor cell population. During postnatal development, Wistar rats will be submitted to early weaning (15th d) and the stomach will be collected to study: a) the expression of molecules by parietal and zymogenic cells, that can be determinant for niche establishment and their signaling- procedures through cell sorting, sequencing and transcriptome; b) the presence and distribution of molecules that determine the niches; c) cell migration; d) myofibroblasts and their secretory activity, and e) the distribution of myofibroblasts in the gastric mucosa under a blockage for glucocorticoid receptor activity, that is known to regulate cell proliferation and cycling compartments. The results will be treated and analyzed through Prism Software and R Studio. (AU)