Role of alamandineE/MrgD interaction in acute kidney injury

• Grant number: 18/25438-2
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: April 01, 2019
• End date: March 31, 2020
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Gerhard Malnic
• Grantee: Regiane Cardoso Castelo Branco
• Supervisor: Adrian Mario Ramos
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz (IIS-FJD), Spain
• Associated to the scholarship: 17/10772-1 - The effects of the Alamandine on the Na+/H+ exchanger in in vivo proximal tubule of spontaneously hypertensive rats, BP.PD

Abstract

Alamandine, a new component of the renin-angiotensin system has been recently identified and characterized and the Mas-related G-protein coupled receptor member D (MrgD) recognized as its receptor. Although cardioprotective effects of alamandine have been described, the significance of this peptide in renal function and kidney pathology, specifically in acute kidney injury (AKI) has not been yet elucidated. Our objective will be to evaluate the functional role of the Alamandine/MrgD couple in the in vivo kidney during the course of the experimental AKI developed in mice. To this aim, the main experimental approaches will include studies of MrgD expression and activity in nephrotoxic, septic and obstructive AKI models developed in wild-type and MrgD-deficient mice. Moreover, direct effects triggered by Alamandine will be investigated under physiologic conditions by the peptide infusion in wild-type mice. Complementary mechanistic studies from the in vivo results will be ascertained in kidney tubular cells and others relevant cell types for AKI, such as vascular cells and fibroblasts. Our data will add new evidence about the importance of the Alamandine/MrgD interaction in the kidney. In addition, our results may indicate a novel therapeutic approach to AKI. (AU)