PEROXISOMAL METABOLISM AS A DRIVER OF POLYCYSTIC KIDNEY DISEASE PROGRESSION

• Grant number: 25/03575-1
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: August 31, 2025
• End date: August 30, 2026
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Niels Olsen Saraiva Câmara
• Grantee: Thaís Alves da Silva
• Supervisor: Pedro Henrique Imenez Silva
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: Erasmus University Rotterdam (EUR), Netherlands
• Associated to the scholarship: 22/16820-6 - Role of peroxisomal biogenesis in the protective effects of caloric restriction in cisplatin-induced Acute Kidney Injury, BP.PD

Abstract

Peroxisomes are vital intracellular organelles involved in important metabolic processes. Mutations in genes that encode peroxisomal biogenesis factors interfere with the proper formation of these organelles. Such disruptions hinder the assembly and function of peroxisomes, resulting in kidney cysts in 70% of cases. Despite the high occurrence of cortical renal cysts in peroxisomal disorders, there has been limited research on peroxisomal metabolism in polycystic kidney diseases, particularly autosomal dominant polycystic kidney disease (ADPKD). ADPKD is mainly caused by mutations in the PKD1 or PKD2 genes and is characterized by the progressive growth of kidney cysts and chronic kidney disease. Although a connection between peroxisomal dysfunction and cyst formation in ADPKD has been suggested, the impact of peroxisomal metabolism on ADPKD remains unclear. Current evidence indicates that the renal cysts observed in patients with peroxisomal disorders may arise from factors outside the kidneys. Furthermore, resident immune cells within renal tissue interact closely with kidney cells. Disruptions to tissue homeostasis can lead to immune cell infiltration, which has been implicated in both acute and chronic kidney diseases, including polycystic kidney disease. The severity of these conditions often correlates with immune cell activity. Importantly, peroxisomes play a critical role in regulating immunometabolism. Human studies have identified differentially expressed peroxisomal genes in the cells lining the cysts, emphasizing the necessity for more research on peroxisomal metabolism in ADPKD. Based on this understanding, we hypothesize that disturbances in peroxisomal biogenesis in immune cells within the renal microenvironment significantly contribute to cyst growth and expansion in ADPKD. To test this hypothesis, we propose to investigate peroxisomal metabolism in organoids derived from ADPKD patients, as well as examining the interactions between peroxisome-deficient immune cells and the organoids. We expect that the data will help to design a more precise medicine for this condition. (AU)