Investigation of PKM2 expression in renal tissue of BTBR wild type and ob/ob males and females

• Grant number: 24/04666-8
• Support Opportunities: Scholarships in Brazil - Master
• Start date: March 01, 2025
• End date: March 31, 2026
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Karina Thieme
• Grantee: Letícia Barreto da Silva
• 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 kidney disease. Both type 1 and type 2 diabetes lead to the development of DKD; however, the increase in the number of individuals with obesity and type 2 diabetes has been one of the major contributors to the rising prevalence, incidence, and number of deaths from chronic kidney disease. The use of experimental models that resemble the course of the disease in humans is necessary, as well as studies that assess differences between different biological sexes. Recent studies have shown that the protein kinase PKM2, a key enzyme in regulating the final limiting step of glycolysis, may serve as a link between glucose metabolism and renal dysfunction, inflammation, and fibrosis in DKD. Preliminary data from the laboratory have shown that renal expression of PKM2 is higher in wild-type females, and it increases in the presence of the metabolic conditions associated with diabetes and obesity. Thus, this study will take an exploratory approach to evaluate the renal gene expression (through RT-qPCR) and protein expression (through immunostaining and immunoblotting) of the protein kinase PKM2 in male and female BTBR wild-type and BTBR ob/ob mice at 8 and 16 weeks of age. With these results, we aim to investigate whether differential expression occurs from the onset of DKD or during its progression. Furthermore, understanding the underlying molecular mechanisms of DKD development and progression and its relationship with sexual dimorphism will pave the way for future therapeutic strategies.