The cGAS-STING pathway: a therapeutic target in diabetes and its complications.

Abstract

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.

• Authors: Wenjie He, Xingrui Mu, Xingqian Wu, Ye Liu, Junyu Deng, Yiqiu Liu, Felicity Han, Xuqiang Nie
• Journal: Burns & trauma (Burns Trauma) Vol. 12 Pg. tkad050 ( 2024) ISSN: 2321-3868 [Print] England
• PMID: 38312740 (Publication Type: Journal Article, Review)
• Copyright: © The Author(s) 2024. Published by Oxford University Press.