Role of cGAS-STING pathway in aging and sexual dimorphism in diabetic kidney disease.
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 towards 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 to non-diabetic 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 proposed the cGAS-STING pathway as an essential contributor to disease development.
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Research summary
The paper investigates the role of the cGAS-STING pathway in the context of aging and sexual dimorphism in diabetic kidney disease, which is relevant to understanding mechanisms that may contribute to age-related diseases. However, it primarily focuses on a specific disease rather than addressing the root causes of aging or lifespan extension. The findings may contribute to the field but do not represent a significant breakthrough or transformative work.
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