DNA methylation enzymes in the kidneys of male and female BTBR ob/ob mice

Author(s)

Pereira, Beatriz Maria Veloso ; de Ponte, Mariana Charleaux ; Luz, Ana Paula Malavolta ; Thieme, Karina

• Document type: Journal article
• Source: FRONTIERS IN ENDOCRINOLOGY; v. 14, p. 10-pg., 2023-04-05.

Abstract

Diabetic kidney disease (DKD) is the leading cause of the end-stage renal disease. Recent studies have shown that epigenetic modifications contribute to alterations in gene expression and the development of DKD. This study aimed to show an expression profile of key DNA (de)methylation enzymes (DNMT, TET proteins) and their differences between sexes under obesity and diabetic condition. Male and female black and tan brachyury (BTBR) ob/ob mice and their corresponding wild-type littermates (BTBR WT) were studied until 16 weeks of age. Metabolic parameters, kidney morphophysiology and the expression of fibrotic markers and epigenetic enzymes were studied in whole kidney tissue or specifically in the glomerulus. The results showed sexual dimorphism in the development of metabolic disease and in kidney morphophysiology. Female mice have a different profile of DNMTs expression in both WT and obese/diabetic condition. Furthermore, metabolic condition negatively modulated the glomerular expression of TET1 and TET3 only in females. To our knowledge, this is the first study that shows a kidney profile of the expression of key (de)methylation enzymes, DNMTs and TETs, in the BTBR ob/ob experimental model of DKD and its association with sex. The knowledge of this epigenetic profile may help future research to understand the pathophysiology of DKD in males and females. (AU)

• FAPESP's process: 19/10583-0 - Epigenetic regulation of TET and Klotho proteins in Glomerular Disease
• Grantee: Beatriz Maria Veloso Pereira
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 18/00573-4 - The role of DNA (hydroxy)methylation in podocytes dysfunction: epigenetic perspectives for the treatment of Chronic Kidney Disease
• Grantee: Karina Thieme
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 21/12782-0 - TNF-alpha and podocyte dysfunction in diabetic kidney disease
• Grantee: Mariana Charleaux de Ponte
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 20/15557-4 - Analysis of Sirtuin 1 activation in restoring autophagy in podocytes
• Grantee: Ana Paula Malavolta Luz
• Support Opportunities: Scholarships in Brazil - Scientific Initiation