The metabolism of Drosophila's renal tubules in calcium oxalate crystallization

• Grant number: 22/01226-1
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: June 01, 2022
• End date: May 31, 2023
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Niels Olsen Saraiva Câmara
• Grantee: Orestes Foresto Neto
• Supervisor: Michael F. Romero
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: Mayo Clinic, Minnesota, United States
• Associated to the scholarship: 19/02893-9 - The hypoxia-inducible factor 1 alpha (HIF-1 alpha) and the metabolism of tubular epithelial cells and podocytes in the development and progression of experimental kidney disease, BP.PD

Abstract

Sudden increase in serum oxalate levels can result in renal calcium oxalate (CaOx) crystals formation, which is a well-known cause of kidney injury. It has been reported that NLRP3 inflammasome activation, necroptosis via RIPK3-MLKL complex, and mitochondrial damage are involved in CaOx-related tubular injury. Changes in renal cell metabolism may also participate in the pathogenesis of CaOx nephropathy. Preliminary data from our laboratory showed that proximal tubular epithelial cells exposed to CaOx crystals had reduced mitochondrial respiration, with concomitant increase in glycolysis capacity. However, the link between alterations in cell metabolism and tubular damage in CaOx nephropathy remains unclear. Drosophila melanogaster develops CaOx crystals in Malpighian tubules upon dietary oxalate supplementation and can be easily genetically modified, providing a rapid model to study nephrolithiasis. In this project, we propose: (i) to assess the metabolism of Malpighian tubule cells facing CaOx crystallization; (ii) to investigate whether changes in metabolic pathways interferes with inflammation/lesions to the tubular cells; and (iii) to verify the impact of knocking down genes related to Drosophila's renal tubular cell metabolism in CaOx-induced tubular damage and tissue repair. (AU)

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)

FORESTO-NETO, ORESTES; TURIN, DANIEL R.; HOLMES, HEATHER L.; REYNOLDS, CARMEN J.; ARNESON, MARIAH L.; CABRERO, PABLO; JAYACHANDRAN, MUTHUVEL; DOW, JULIAN A. T.; LIESKE, JOHN C.; FURROW, EVA; et al. The Anoctamin 4 Homolog Limits Bacterial Infection and Calcium Oxalate Crystallization in Drosophila Renal Tubules. PHYSIOLOGY, v. 38, p. 2-pg., 2023-05-01. (22/01226-1)