The role of metabolic memory in the development of diabetic nephropathy

• Grant number: 12/22190-3
• Support Opportunities: Regular Research Grants
• Duration: May 01, 2013 - October 31, 2015
• Field of knowledge: Biological Sciences - Biochemistry
• Principal Investigator: Ana Paula de Melo Loureiro
• Grantee: Ana Paula de Melo Loureiro
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Diabetes mellitus is considered a serious global health problem, and its complications have a major impact on population mortality. Diabetic nephropathy is a major complication of metabolic disease, characterized primarily by a progressive decline in the rate of glomerular filtration, persistent proteinuria, and hypertension. Several mechanisms have been proposed as important in the pathogenesis and progression of diabetic nephropathy. Hyperglycemia is closely associated with oxidative stress, with increase in pro-inflammatory cytokines such as IL-1, IL-6 and TNF-±, growth factors, such as TGF-², and formation of advanced glycation end products. Considering the fact that even after glycemic control there is the occurrence of diabetic complications, recent studies have proposed the phenomenon known as metabolic memory to explain this fact. From this perspective, this study will evaluate the modulation of a series of markers related or possibly related to diabetic nephropathy in conditions of hyperglycemia and early and late glycemic control by the oral antidiabetic agent metformin. Markers related to oxidative stress (protein expression of SIRT-1, AMPK, Bax, TGF-b, MKK 3/6, MKP-1 and p38), inflammation (IL-6, TNF-a, NF-kB) and the advanced glycation process (glycated hemoglobin and N-(carboxymethyl)lysine) will be evaluated in a model of diabetic rats, as well as the expression of target genes (PPARGC1A, TGF-², TSP-1, MKP-1 and UNC13B) and their possible epigenetic regulation (methylation of CpG islands) with or without control of hyperglycemia. The aim here is thus to elucidate new pathways involved in the process of metabolic memory that have an important role in the development of diabetic nephropathy, in order to contribute to its control. (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)

FALCAO DE OLIVEIRA, ANTONIO ANAX; DE OLIVEIRA, TIAGO FRANCO; DIAS, MICHELLE FRANCINI; GENNARI MEDEIROS, MARISA HELENA; DI MASCIO, PAOLO; VERAS, MARIANA; LEMOS, MIRIAM; MARCOURAKIS, TANIA; NASCIMENTO SALDIVA, PAULO HILARIO; MELO LOUREIRO, ANA PAULA. Genotoxic and epigenotoxic effects in mice exposed to concentrated ambient fine particulate matter (PM2.5) from SAo Paulo city, Brazil. PARTICLE AND FIBRE TOXICOLOGY, v. 15, OCT 19 2018. (12/08617-4, 12/08616-8, 11/09891-0, 12/22190-3, 12/21636-8, 13/07937-8)

DE OLIVEIRA, TIAGO FRANCO; FELCAO DE OLIVEIRA, ANTONIO ANAX; LEMOS, MIRIAM; VERAS, MARIANA; NASCIMENTO SALDIVA, PAULO HILARIO; GENNARI DE MEDEIROS, MARISA HELENA; DI MASCIO, PAOLO; DE MELO LOUREIRO, ANA PAULA. Quantification of three DNA Lesions by Mass Spectrometry and Assessment of Their Levels in Tissues of Mice Exposed to Ambient Fine Particulate Matter. JOVE-JOURNAL OF VISUALIZED EXPERIMENTS, n. 147, MAY 2019. (13/07937-8, 11/09891-0, 12/08617-4, 12/21636-8, 12/08616-8, 12/22190-3)