Apelinergic signaling implications on renal sodium and water transport: the role of ischemia/reperfusion

• Grant number: 22/05371-6
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: January 01, 2023
• End date: December 31, 2024
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Maria Oliveira de Souza
• Grantee: Guilherme Lopes Gonçalves
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The apelinergic system plays an essential role in cardiovascular physiology and fluid and electrolyte balance has been the subject of recent studies involving the kidneys. Apelins are endogenous peptides that interact with the G protein coupled APJ receptor and exert effects on glomerular hemodynamics as well as tubular function. Recently, the activation of the apelinergic system has been described as a possible alternative to attenuate the deleterious effects of acute kidney injury (AKI) resulting from renal ischemia/reperfusion (I/R), a common hospital condition that results in a high mortality rate and may be associated with episodes of sepsis, shock, cardiovascular surgery, or transplants. Even so, considering the contribution of apelins, the role of sodium and water transporters in the physiological context, as well in AKI resulting from I/R is still unclear. Thus, our objective is to investigate the effects of the signaling pathway activated by apelin-13 on the transport of sodium and water, in a physiological and pathological context, using in vitro and in vivo approaches. For this, lines of proximal tubular cells (IRPTC), from the thick ascending loop of Henle (ST-1), from the distal convoluted tubule (209/MDCT) and from the collecting duct (MDCK) will be treated with apelin-13 (in standardized concentrations) for 30 min and 24 h. On the animal model of I/R, the influence of previous treatment with apelin-13 will be evaluated in mice submitted to bilateral renal ischemia for 30 min and euthanized after 48h of reperfusion, considering renal function, creatinine clearance and sodium excretion. The activity of the sodium/hydrogen exchanger isoform 3 (NHE3), as well as the cotransporter NKCC2 will be evaluated by fluorescence microscopy. Protein expression will be analyzed by western blotting. By immunofluorescence, the location and expression of sodium transporters will be investigated, as well as the water reabsorption pathway mediated by aquaporin 2 (AQP2) by immunoprecipitation. With the results of the project, we hope to establish a better understanding of the molecular mechanisms involved in the renal apelinergic system as well as new possibilities for the treatment of renal diseases. (AU)