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.本研究针对2型糖尿病肾病（Type 2 Diabetic Nephropathy，T2DN）大鼠，探究了不同性别个体的cGAS-STING炎症通路活性差异，及其对糖尿病肾病（Diabetic Kidney Disease，DKD）病程进展的影响。本研究纳入了年轻与老年的雄性、雌性T2DN大鼠。研究结果显示，cGAS-STING通路在雄性与雌性T2DN大鼠中呈现出显著不同的蛋白质表达谱，且该表达差异随衰老进程显著加剧。相较于同年龄段的雌性T2DN大鼠，雄性个体的促炎基因表达水平显著升高，且该表达差异随年龄增长进一步加重。值得注意的是，针对不同年龄、不同性别的T2DN大鼠肾皮质开展的全转录组RNA测序（RNA-Seq）分析，揭示了多个核心调控分子，其中包含cGAS-STING通路中的关键基因。本研究阐明了DKD发生发展过程中复杂的性别差异，并提出cGAS-STING通路在DKD发病机制中发挥基础性作用。