Evaluation of treatment with liraglutide and SGLT2 inhibitors in inflammation mediated by the action of microRNAS 21, 145 and 34A on the HIF1-alpha factor in proximal cells (HK-2) subject to oxygen deprivation

• Grant number: 24/06309-8
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: June 01, 2024
• End date: May 31, 2027
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Marcelo Costa Batista
• Grantee: Julia Cristine Oliveira
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated research grant: 19/25493-6 - Obesity: pathophysiology and related therapeutic strategies, AP.TEM

Abstract

Visceral obesity, the core of Metabolic Syndrome (MS), is conceived as a pathophysiological basis related to the epidemic incidence of cardiovascular events. It has been suggested that MS is a programmable disease, characterized by changes epiggenetics of vital genes when exposed to stress of different shades, such as hypoxia associated with inflammation. Epigenetic modifications participate in susceptibility to chronic kidney disease and it has been investigated how the environment interacts with the renal cell epigenome to contribute to renal damage. Changes in the expression of microRNAs can result in changes in the pattern of genes that control a series of biological processes, such as: inflammation, lipid metabolism, insulin resistance and adipogenesis. The use of GLP-1 (glucagon-like peptide 1) agonists and, more recently, renal tubular glucose transport inhibitors (iSGLT 2) has been related to greater preservation of renal function in patients with kidney disease. Considering the importance of cellular adaptive processes in the pathophysiology of renal tubular injury induced by obesity, the objective of this study is to evaluate the effect of treatment with the GLP1 agonist in association with an sGLT2 inhibitor on the modulation of microRNAs 21, 145 and 34a on the expression of mediators inflammatory processes in cultured proximal cells (HK-2) subjected to oxygen deprivation and stimulated with leptin. (AU)