Advanced search
Start date
Betweenand

"interaction between HIF-1 and short-chain fatty acids in the intestine: what is the role of HIF-1 acetylation? "

Grant number: 16/23142-3
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): March 01, 2017
Effective date (End): February 28, 2021
Field of knowledge:Biological Sciences - Physiology
Principal Investigator:Marco Aurélio Ramirez Vinolo
Grantee:Renan Oliveira Corrêa
Home Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Associated research grant:12/10653-9 - Role of short chain fatty acids and their receptor (GPR43) in the immune response to anaerobic bacteria in vivo and in vitro, AP.JP
Associated scholarship(s):19/02640-3 - Role of the high-fiber diet on the function of the intestinal stem cells and their niche, BE.EP.DR

Abstract

Short-chain fatty acids (SCFAs) are products from the intestinal microbiota mainly produced by the fermentation of dietary fibers. SCFAs are found at high concentrations in the colon in where they play a fundamental energetic role in the epithelial cells, show important immunomodulatory effects, as well as they help to maintain the intestinal homeostasis through the regulation of the proliferation/apoptosis of intestinal epithelial cells (IECs) and the production of host defense peptides, both effects that seem to be involved with the stabilization of the ± subunit of the hypoxia-inducible factor 1 (HIF-1). Recent studies have related the energetic role of SCFAs with the increased (indirect) activation of HIF-1± in the IECs, even though they did not consider their other mechanisms of action. With that, the goal of this project is to investigate the participation and the importance of HIF-1 in the effects of the SCFAs produced under physiological conditions (diets with different amounts of fiber) in the IECs, as well as to elucidate the possible mechanism of direct interaction between the SCFAs and HIF-1. For that, we will use in vivo models (tissue-specific knockout animals for HIF-1 and/or Vhl) and in vitro models (intestinal organoids), in which we will perform molecular analysis including Western blotting, immunofluorescence, RT-PCR, metagenomics of 16S RNA, mass spectrometry, RNA sequencing, immunoprecipitation of chromatin with sequencing (ChIP-Seq), analysis of HDAC inhibitors and immunohistological analysis of the intestine after a model of inducible colitis by C. difficile.

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
FACHI, JOSE LUIS; FELIPE, JAQUELINE DE SOUZA; PRAL, LAIS PASSARIELLO; DA SILVA, BRUNA KARADI; CORREA, RENAN OLIVEIRA; PEREIRA DE ANDRADE, MIRELLA CRISTINY; DA FONSECA, DENISE MORAIS; BASSO, PAULO JOSE; SARAIVA CAMARA, NIELS OLSEN; DE SALES E SOUZA, ERICKA LORENNA; MARTINS, FLAVIANO DOS SANTOS; SATO GUIMA, SUZANA EIKO; THOMAS, ANDREW MALTEZ; SETUBAL, JOAO CARLOS; MAGALHAES, YULI THAMIRES; FORTI, FABIO LUIS; CANDREVA, THAMIRIS; RODRIGUES, HOSANA GOMES; DE JESUS, MARCELO BISPO; CONSONNI, SILVIO ROBERTO; FARIAS, ALESSANDRO DOS SANTOS; VARGA-WEISZ, PATRICK; RAMIREZ VINOLO, MARCO AURELIO. Butyrate Protects Mice from Clostridium difficile-Induced Colitis through an HIF-1-Dependent Mechanism. CELL REPORTS, v. 27, n. 3, p. 750+, APR 16 2019. Web of Science Citations: 3.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.