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 Opportunities: Scholarships in Brazil - Doctorate
• Start date: March 01, 2017
• End date: February 28, 2022
• Field of knowledge: Biological Sciences - Physiology - General Physiology
• Principal Investigator: Marco Aurélio Ramirez Vinolo
• Grantee: Renan Oliveira Corrêa
• Host 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

(4)

(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; et al. 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. (17/01451-7, 12/10653-9, 16/23142-3, 13/06810-4, 14/03002-7, 15/01507-7, 18/01753-6, 15/06134-4, 17/25679-7, 17/06577-9, 18/02208-1, 17/26366-2, 17/16280-3)

CORREA, RENAN OLIVEIRA; CASTRO, POLLYANA RIBEIRO; FACHI, JOSE LUIS; NIRELLO, VINICIUS DIAS; EL-SAHHAR, SALMA; IMADA, SHINYA; PEREIRA, GABRIEL VASCONCELOS; PRAL, LAIS PASSARIELLO; PEREIRA ARAUJO, NATHALIA VITORIA; FERNANDES, MARIANE FONT; et al. Inulin diet uncovers complex diet-microbiota-immune cell interactions remodeling the gut epithelium. MICROBIOME, v. 11, n. 1, p. 25-pg., 2023-04-26. (16/23142-3, 21/06572-2, 19/06372-3, 19/16113-5, 19/02640-3, 18/15313-8, 20/02919-5, 17/16280-3, 20/14071-0, 21/00393-9, 17/06577-9, 20/13689-0, 21/05269-4, 20/02312-3, 18/10165-0, 20/00311-0)

ROCHA, ANDREA LIVIA; DE LIMA, TANES IMAMURA; DE SOUZA, GERSON PROFETA; CORREA, RENAN OLIVEIRA; FERRUCCI, DANILO LOPES; RODRIGUES, BRUNO; LOPES-RAMOS, CAMILA; NILSSON, DANIEL; KNITTEL, THIAGO LEITE; CASTRO, POLLYANA RIBEIRO; et al. Enoxacin induces oxidative metabolism and mitigates obesity by regulating adipose tissue miRNA expression. SCIENCE ADVANCES, v. 6, n. 49, DEC 2020. (10/52557-0, 17/01184-9, 18/15313-8, 16/23142-3, 17/07975-8, 16/24163-4, 15/01316-7, 16/12294-7)

PRAL, LAIS P.; FACHI, JOSE L.; CORREA, RENAN O.; COLONNA, MARCO; VINOLO, MARCO A. R.. Hypoxia and HIF-1 as key regulators of gut microbiota and host interactions. TRENDS IN IMMUNOLOGY, v. 42, n. 7, p. 604-621, JUL 2021. (16/23142-3, 17/06577-9, 18/02208-1, 18/15313-8)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

CORRÊA, Renan Oliveira. The impact of high-fiber diets in the colonic epithelial microenvironment. 2022. Doctoral Thesis - Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia Campinas, SP.