cGAS-STING signaling in ischemic diseases

•DNA initiates the immune response by activating the cGAS-STING axis.•cGAS-STING signaling is widely involved in the regulation of cell fate.•The cGAS-STING pathway is closely associated with ischemic damage to organs. Double stranded DNA (dsDNA) is known to act as a damage‐associated molecular pattern (DAMP) that stimulates the body's innate immune response. In general, cyclicGMP-AMP(cGAMP)synthase(cGAS), a DNA sensor, detects these disease‐causing DNA and activates the stimulator of interferon gene (STING), which in turn phosphorylates interferon regulatory factor 3 (IRF3), triggering the synthesis of type I interferon (IFN). During this process, the cGAS‐STING pathway interacts with different modes of cell death, including autophagy, apoptosis, pyroptosis, and necroptosis. Importantly, cGAS might get stimulated by self‐DNA, such as nuclear DNA (nuDNA) and mitochondrial DNA (mtDNA), which ensures a close association between the cGAS‐STING signaling pathway and autoimmune responses. Following an ischemic attack, damaged or necrotic cells release large amounts of self‐DNA that subsequently activate cGAS, resulting in a range of consequences related to an injury. The present study presents an overview of studies focused on cGAS‐STING signaling and cell death, and summarizes the findings of this pathway with regard to ischemia or ischemia/reperfusion (I/R) in different organs of the body, including heart, brain, liver, kidney, and intestine.