Role of PPAR gamma in inflammation and glucose transport in Caco-2 cells

• Grant number: 18/21964-1
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Effective date (Start): July 22, 2019
• Effective date (End): March 24, 2020
• Field of knowledge: Biological Sciences - Physiology - General Physiology
• Principal Investigator: José Cesar Rosa Neto
• Grantee: Luana Amorim Biondo
• Supervisor: Philip Charles Calder
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Research place: University of Southampton, England
• Associated to the scholarship: 16/06753-9 - Role of PPAR³ in the imunometabolic effects of adipose tissue and macrophages, in induced colon tumor model., BP.DR

Abstract

Colorectal cancer compromises large bowel and rectum. Approximately 20% of patients with inflammatory bowel disease (IBD) develop colon cancer and this population has twofold increase in mortality. IBD is a chronic inflammatory condition of the gastrointestinal epithelium due to alterations in immune system reactivity. In colorectal colitis-associated tumors and in IBD, there is a disruption in pro- and anti-inflammatory responses and the intestinal mucosa secretes high concentrations of pro-inflammatory cytokines. Inflammatory cytokines can regulate carbohydrate metabolism.Peroxisome proliferator-activated receptor gamma (PPAR³) is a nuclear receptor highly expressed in differentiated epithelial cells of the colon, including in the Caco-2 cell line, which controls the expression of large number of regulatory genes in glucose homeostasis and inflammation.Therefore, the aim of this study is to characterize the effects of a PPAR³ agonist and antagonist on inflammation and on glucose metabolism of the Caco-2 cell line. For this, human epithelial Caco-2 cells will be incubated with 2% dextran sodium sulfate (DSS) and the cells will be treated with PPAR³ agonist (pioglitazone 50 and 300uM) and PPAR³ antagonist (GW9662 5 and 10 uM).The methods to be used are: trans-epithelial electrical resistance to determine cellular permeability; glucose transport assay to check the passage through the epithelial monolayer; multiplex ELISA to measure changes in protein content of glucose transporters and inflammatory markers; real time-PCR to analyze changes in gene expression of glucose transporters and inflammatory markers; flow cytometry to understand any additional effects of PPAR³ on apoptosis and cell-cycle checkpoints.

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)

SILVEIRA, LOREANA SANCHES; BIONDO, LUANA AMORIM; DE SOUZA TEIXEIRA, ALEXANDRE ABILIO; DE LIMA JUNIOR, EDSON ALVES; CASTOLDI, ANGELA; SARAIVA CAMARA, NIELS OLSEN; FESTUCCIA, WILLIAN T.; ROSA-NETO, JOSE CESAR; LIRA, FABIO SANTOS. Macrophage immunophenotype but not anti-inflammatory profile is modulated by peroxisome proliferator-activated receptor gamma (PPAR gamma) in exercised obese mice. EXERCISE IMMUNOLOGY REVIEW, v. 26, p. 94-106, 2020. (18/21964-1, 13/25310-2, 14/01246-6, 16/01409-8)