The relationship between NRLP3 inflammasome and glycolytic metabolism of tubular epithelial cells in the development of renal fibrosis

• Grant number: 18/17513-4
• Support type: Scholarships in Brazil - Post-Doctorate
• Effective date (Start): October 01, 2018
• Effective date (End): September 30, 2020
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Niels Olsen Saraiva Câmara
• Grantee: Ingrid Kazue Mizuno Watanabe
• Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 17/05264-7 - Cell metabolism, microbiota and immune system: new paradigms in renal diseases physiopathology, AP.TEM

Abstract

Renal fibrosis is a progressive detrimental connective tissue deposition on the kidney parenchyma, leading inevitably to renal function deterioration, dialysis dependence, and, ultimately, kidney transplantation. Despite accumulating knowledge of pathways and molecules involved in the fibrogenesis, little is known about which cellular mechanisms orchestrate this process. Recently, new evidences reveal that altered glycolytic and oxidative metabolisms of proximal tubular epithelial cells (PTECs) are intimately involved in the renal fibrotic process. NRLP3 inflammasome is a multiprotein platform that connects inflammatory pathways and metabolic changes. Based on that, our hypothesis is that metabolic changes are the common pathway of proinflammatory stimuli sensed by NLRP3 inflammasome and the development of fibrosis. PTECs will be isolated from wild type and NRLP3 knockout mice aiming to study the role of NRLP3 inflammasome in the cellular energetic metabolism in the presence of uric acid and TGF-b using different techniques, such as Seahorse, Western blotting, flow cytometry and CHIP-PCR. In addition to vitro experiments, the project includes experimental models of unilateral ureter obstruction in wild type and knockout mice aiming to evaluate the role of NRLP3 and metabolism-related factors in the onset and development of kidney disease.

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)

ANDRADE-OLIVEIRA, VINICIUS; FORESTO-NETO, ORESTES; MIZUNO WATANABE, INGRID KAZUE; ZATZ, ROBERTO; SARAIVA CAMARA, NIELS OLSEN. Inflammation in Renal Diseases: New and Old Players. FRONTIERS IN PHARMACOLOGY, v. 10, OCT 8 2019. Web of Science Citations: 1.