Role of cGAS/STING pathway in aging and sexual dimorphism in diabetic kidney disease. JCI Insight 2024 Nov 26;10(1)
Date
11/26/2024Pubmed ID
39589791Pubmed Central ID
PMC11721291DOI
10.1172/jci.insight.174126Scopus ID
2-s2.0-85214325933 (requires institutional sign-in at Scopus site)Abstract
Diabetic kidney disease (DKD) is the leading cause of chronic renal pathology. Understanding the molecular underpinnings of DKD is critical to designing tailored therapeutic approaches. Here, we focused on sex differences and the contribution of aging toward the progression of DKD. To explore these questions, we utilized young (12 weeks old) and aged (approximately 50 weeks old) type 2 diabetic nephropathy (T2DN) rats. We revealed that the cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) pathway was upregulated in T2DN rats compared with nondiabetic Wistar rats and in type 2 diabetic human kidneys. The activation of the cGAS/STING signaling pathway exhibited distinct protein expression profiles between male and female T2DN rats, with these differences becoming more pronounced with aging. RNA-Seq analysis of the kidney cortex in both male and female T2DN rats, at both younger and older ages, revealed several key molecules, highlighting crucial genes within the cGAS/STING pathway. Thus, our study delved deep into understanding the intricate sexual differences in the development and progression of DKD and we propose the cGAS/STING pathway as an essential contributor to disease development.
Author List
Khedr S, Dissanayake LV, Alsheikh AJ, Zietara A, Spires DR, Kerketta R, Mathison AJ, Urrutia R, Palygin O, Staruschenko AAuthor
Angela Mathison PhD Assistant Professor in the Surgery department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AgingAnimals
Diabetes Mellitus, Type 2
Diabetic Nephropathies
Female
Humans
Kidney
Male
Membrane Proteins
Nucleotidyltransferases
Rats
Rats, Wistar
Sex Characteristics
Signal Transduction
