Diabetic wound healing (DWH) represents a major complication of diabetes where inflammation is a key impediment to proper healing. The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway has emerged as a central mediator of inflammatory responses to cell stress and damage. However, the contribution of cGAS-STING activation to impaired healing in DWH remains understudied. In this review, we examine the evidence that cGAS-STING-driven inflammation is a critical factor underlying defective DWH. We summarize studies revealing upregulation of the cGAS-STING pathway in diabetic wounds and discuss how this exacerbates inflammation and senescence and disrupts cellular metabolism to block healing. Partial pharmaceutical inhibition of cGAS-STING has shown promise in damping inflammation and improving DWH in preclinical models. We highlight key knowledge gaps regarding cGAS-STING in DWH, including its relationships with endoplasmic reticulum stress and metal-ion signaling. Elucidating these mechanisms may unveil new therapeutic targets within the cGAS-STING pathway to improve healing outcomes in DWH. This review synthesizes current understanding of how cGAS-STING activation contributes to DWH pathology and proposes future research directions to exploit modulation of this pathway for therapeutic benefit.

中文翻译：

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cGAS-STING 通路：糖尿病及其并发症的治疗靶点

糖尿病伤口愈合 (DWH) 是糖尿病的主要并发症，其中炎症是正常愈合的主要障碍。环 GMP-AMP 合酶 (cGAS)-干扰素基因刺激剂 (STING) 信号通路已成为细胞应激和损伤炎症反应的中心介质。然而，cGAS-STING 激活对 DWH 愈合受损的影响仍有待研究。在这篇综述中，我们检查了 cGAS-STING 驱动的炎症是 DWH 缺陷的关键因素的证据。我们总结了揭示糖尿病伤口中 cGAS-STING 通路上调的研究，并讨论了这种现象如何加剧炎症和衰老并扰乱细胞代谢从而阻碍愈合。 cGAS-STING 的部分药物抑制在临床前模型中显示出抑制炎症和改善 DWH 的前景。我们强调了 DWH 中有关 cGAS-STING 的关键知识差距，包括其与内质网应激和金属离子信号传导的关系。阐明这些机制可能会揭示 cGAS-STING 通路中的新治疗靶点，以改善 DWH 的愈合结果。这篇综述综合了目前对 cGAS-STING 激活如何促进 DWH 病理学的理解，并提出了利用该途径的调节以获得治疗益处的未来研究方向。