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Effect of inulin and Short-Chain Fatty Acids (SCFAs) on Hypoxia-Inducible Factor 1 (HIF-1) and its target genes in epithelial cells and intestinal stem cells

Grant number: 20/02919-5
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): April 01, 2020
Status:Discontinued
Field of knowledge:Biological Sciences - Immunology - Applied Immunology
Principal researcher: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
Associated scholarship(s):22/04895-1 - Characterization of the inulin effects on microbiota and hypoxia and its relationship with HIF-1a stabilization in the colon of mice, BE.EP.PD

Abstract

Short-Chain Fatty Acids (SCFAs) from the fermentation of fiber-rich diets by the intestinal microbiota play important modulatory functions in the intestinal epithelium. These metabolites regulate genes involved in the energy metabolism of Intestinal Epithelial Cells (IECs) by stimulating oxygen consumption and, consequently, the activation of Hypoxia-Inducible Factor (HIF). Several studies have related the role of fiber-rich diets and a healthy microbiota in the stabilization of HIF-1 and expression of its target genes in IECs. Although these studies have brought important insights into this field of knowledge, the mechanisms and molecular interactions by which these metabolites act on the direct expression of HIF-1 in IECs and Intestinal Stem Cells (ISCs) are not well established. Preliminary studies by our research group indicate that HIF-1± and its target genes act by reducing the increase in cell proliferation in the colon in response to fiber-rich diets, indicating an important regulatory role of this factor on intestinal homeostasis. In this project, we intend, therefore, to determine the direct effects that an inulin-rich diet exerts on the stabilization of HIF-1 in IECs and ISCs in mice, as well as the mechanisms and factors associated with these interactions. The data obtained in this project will help to understand how HIF-1± acts in homeostasis contexts and, additionally, may provide support for the understanding of how pathophysiological processes are established in the intestinal epithelium. (AU)

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