Role of cGAS-STING pathway in aging and sexual dimorphism in diabetic kindey disease
We investigated the cGAS-STING inflammatory pathway differential activity among both sexes in T2DN rats and its impact on the temporal progression of the diabetic kidney disease. Here we used both male and female old and young T2DN rats. The cGAS-STING pathway presented distinct protein expression profiles between male and female T2DN rats, which significantly intensify with aging. In male T2DN rats, pro-inflammatory genes are particularly heightened in comparison to female rats of similar age, and such levels are further exacerbated with age. Interestingly, a comprehensive RNA-Seq analysis conducted in the kidney cortex of both sexes of T2DN rats, in younger and older ages, disclosed several central molecules, with crucial genes identified within the cGAS-STING pathway. Our study showed the intricate sexual differences in the development and progression of DKD and proposed the fundamental role of cGAS-STING pathway in disease development. Overall design: Animals used for the current study were young and old male and female. The animals were euthanized by opening thoracic cavity under deep anesthesia (2% (vol/vol) isoflurane), and both kidneys were collected. One kidney was stored in Formalin for histological analyses, and the other was snap-frozen for molecular analyses. Transcriptomics was done using kidney cortex from each time point for both sexes old and young groups.