Role of TNF-± in glomerular injury in male and female animals with obesity and diabetes

• Grant number: 23/09403-2
• Support Opportunities: Regular Research Grants
• Start date: February 01, 2024
• End date: January 31, 2026
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Karina Thieme
• Grantee: Karina Thieme
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease in the world. Inflammation has an early onset in most renal failures, initially as a protective mechanism. However, this inflammatory state can exceed the physiological limit, becoming chronic and with undesirable systemic consequences. The pro-inflammatory and pro-fibrotic processes that occur during the development and progression of DKD result from metabolic changes, hyperfiltration, oxidative stress and increased inflammation. Infiltration of inflammatory cells and increased expression of cytokines, chemokines, adhesion molecules and growth factors contribute to local inflammation and tissue injury. In recent years, epigenetics has emerged as a new way of looking at the determinants of several diseases, including DKD. Recent studies have demonstrated the importance of changes in the epigenome, in particular post translational histone modifications, in the expression of numerous genes involved in the process of kidney injury. Thus, in light of the information presented here, the general aim of this study is to explore the participation of glomerular inflammation, mediated by TNF-± and the epigenetic mechanisms involved in renal injury in an in vivo model of DKD associated with obesity, in male and female mice. With the results, we hope to elucidate new molecular mechanisms that contribute to the development and progression of DKD, supporting new therapeutic proposals. (AU)