Characterization of peri-cryptal extracellular matrix and the role of myofibroblasts in intestinal stem cell niche: effects of early weaning

• Grant number: 21/14633-1
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: June 01, 2022
• End date: February 28, 2026
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Patrícia Gama
• Grantee: Marcos Aurélio Santos da Costa
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The gastrointestinal tract main functions are digestion and absorption of nutrients, which are mediated by epithelial cells in the mucosa. In the intestine, the growth, maintenance and regeneration depend on the activity of crypt stem cells, which are in a niche at the bottom of the crypt. This niche contains the Paneth cell population. and it is sorrounded by the lamina propria that hosts two specific niches- the cellular one (fibroblasts, telocytes and myofibroblasts) and structural niche (extracellular matrix). However, the behavior of such microenvironment against/during changes of feeding behavior is unknown. By considering that early weaning can induce morphophysiological changes in the gastrointestinal tract and there can be a modification of cell renewal/growth and maintenance, it is necessary to evaluate the effects of breastfeeeding interruption on the cellular and structural niches. So, our aim is to study how early weaning influneces the distribution of: collagens, both in the basal lamina and intersticial matrix, proteoglicans, glycosaminoglicans and glycoproteins as well as the cellular components (telocytes and myofibrblasts). The role of myofibroblasts, the organization of ECM and cell signaling will investigated in rats under regular breastfeeding or early weaned. We will evaluate the immediate and late responses in adult life, and to that, Wistar rats will be EW and the jejunum will be collected for morphological and molecular protocols. All results will be described and analyzed statistically. (AU)