PROFILE OF MIDKINE AND NLRP3 EXPRESSION IN THE CENTRAL NERVOUS SYSTEM AND KIDNEY IN AN ANIMAL MODEL OF DIABETES MELLITUS

• Grant number: 24/12584-1
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: September 01, 2024
• End date: August 31, 2025
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Glaucia Raquel Luciano da Veiga
• Grantee: Estella Freitas Silvestri
• Host Institution: Centro Universitário FMABC (FMABC). Santo André , SP, Brazil

Abstract

Introduction: Type 2 diabetes mellitus (DM2) is a globally prevalent metabolic condition characterized by chronic elevation of blood glucose and insulin resistance. The International DiabetesFederation (IDF) estimates a 65% increase in DM2 cases by 2045, affecting 9.9% of the world's population. Biomarkers such as estimated glomerular filtration rate (eGFR) and albuminuria are usedin diagnosis, although studies have identified patients with reduced renal function without significant albumin excretion. Midkine (MK), a protein expressed by the MDK gene, performs various cellularfunctions and is regulated by retinoic acid and Hypoxia-Inducible Factor 1-Alpha (HIF-1±). In pathological contexts such as inflammation and tissue injury, MK expression increases, particularly in tissues like endothelium, cerebral cortex, and myocardium. The NLRP3 inflammasome is implicated in DM2 pathogenesis, associated with chronic inflammation and renal complications such as fibrosisand tubular dysfunction. NLRP3 activation can lead to the release of inflammatory cytokines and inflammation-mediated cell death (pyroptosis). Its expression and activity are elevated in patients withdiabetic renal disease (DRD). Objectives: This study aims to investigate the relationship between NLRP3 and MK gene expression in a rat model of DM2, aiming to understand their impact on therenal and central nervous systems (CNS). Additionally, it seeks to explore the potential of these genes as biomarkers for DRD development, providing valuable insights for the early diagnosis and treatment of this DM2 complication.