Advanced search
Start date
Betweenand

Relevance of the FFAR2 receptor on the biological responses of stem cells and Intestinal Epithelial Cells (IECs) during inflammatory conditions

Grant number: 20/02919-5
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): April 01, 2020
Effective date (End): March 31, 2022
Field of knowledge:Biological Sciences - Immunology - Applied Immunology
Principal Investigator:Marco Aurélio Ramirez Vinolo
Grantee:Pollyana Ribeiro Castro
Home Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Associated research grant:18/15313-8 - Investigation of the molecular mechanisms involved in the interaction between microbiota-derived metabolites and host cells during inflammation, AP.JP2

Abstract

The FFAR2 receptor is highly expressed in myeloid and epithelial cells and its activation by Short-Chain Fatty Acids (SCFAs) modulates the biological activity and metabolism of immune cells, Intestinal Epithelial Cells (IECs) and Intestinal Stem Cells (ISCs). In IECs, the activation of the FFAR2 receptor by SCFAs has been associated with the production of proinflammatory cytokines and antimicrobial peptides. The effect that the activation of FFAR2 by SCFAs has on ISCs is still not well understood, although some studies indicate that the exposure of intestinal organoids to acetate, a type of SCFA, induces an increase in the expression of Lgr5, a stem cell marker. Despite the evidence cited, the molecular mechanisms involved in the responses triggered by the activation of FFAR2, exposure to SCFAs and antimicrobial peptides in IECs and ISCs during infection by pathogens and in the presence of inflammation have not been extensively investigated. Thus, the aim of this project is to examine the role of FFAR2 during transcriptional and metabolic adaptations of IECs and ISCs during intestinal inflammation induced by C. difficile in mice. In addition, it is intended to establish the mechanisms associated with the cellular responses of IECs and ISCs in intestinal organoids cultured in the presence of AGCCs, inflammatory mediators and C. difficile toxins. (AU)