Effect of caloric restriction on cGAS-STING signaling on Acute Kidney Injury in Zebrafish

• Grant number: 22/12833-6
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: July 01, 2023
• End date: November 30, 2026
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Niels Olsen Saraiva Câmara
• Grantee: Barbara Nunes Padovani
• Host 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

Caloric restriction (CR) is defined as the decrease in calorie intake of approximately 20 to 40%, without the deprivation of essential nutrients. Numerous beneficial effects are reported in individuals who use calorie restriction, such as, slowing immune senescence, improving metabolic health and the prevention of diseases related to ageing, including cancer, diabetes, cardiovascular and neurodegenerative diseases. Kidney diseases, especially acute kidney injury (AKI), results in increased of oxidative stress in kidney cells and the development of an inflammatory process in the kidneys. Currently, there is no preventive treatment for AKI, so it is necessary to study mechanisms that can act on renoprotection and to avoid or mitigate the effects of this condition. From this, a nephroprotective effect of CR against renal injury in animal models has been observed, moreover, it has been seen that nutritional adjustment may have prophylactic or therapeutic effects in cancer. The existence of a connection between caloric restriction and kidney injury generates a range of possible and candidate genes to be exploited as therapeutic targets. During the progression of AKI, mitochondrial DNA released into the cytosol by mitochondrial dysfunction is recognized by different receptors, including STING (Stimulator of interferon genes). This protein is a pattern recognition receptor that is part of the cGAS-STING signaling pathway and that acts as a DNA sensor by recognizing disturbances in homeostasis such as the accumulation of nucleic acids under stress conditions or after infections, acting on the release of type I interferon and other pro-inflammatory cytokines. Taking into account that mitochondrial damage and activation of the cGAS-STING pathway induce tubular inflammation and progression of AKI, our hypothesis is that CR will improve mitochondrial function and decrease DNA damage in addition to acting on its repair through the activation of the antioxidant system. Therefore, the project aims to study the effect of caloric restriction on acute kidney injury, focusing on the STING protein for a better understanding of the mechanisms involved during the process. Overall, studying possible molecules or signaling pathways that contribute to protective effects can be an effective strategy to know how to control kidney damage and disease development. (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)

PADOVANI, BARBARA NUNES; FENERO, CAMILA MORALES; PAREDES, LAIS CAVALIERI; DO AMARAL, MARIANA ABRANTES; DOMINGUEZ-AMOROCHO, OMAR; CIPELLI, MARCELLA; GOMES, JULIANA MOREIRA MENDONCA; DA SILVA, ELOISA MARTINS; SILVA, LUISA MENEZES; DE SOUZA VIEIRA, RAQUEL; et al. Cisplatin Toxicity Causes Neutrophil-Mediated Inflammation in Zebrafish Larvae. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 25, n. 4, p. 16-pg., 2024-02-01. (17/05264-7, 15/21644-9, 22/12833-6)