111614
论文已发表
注册即可获取德孚的最新动态
IF 收录期刊
- 3.4 Breast Cancer (Dove Med Press)
- 3.2 Clin Epidemiol
- 2.6 Cancer Manag Res
- 2.9 Infect Drug Resist
- 3.7 Clin Interv Aging
- 5.1 Drug Des Dev Ther
- 3.1 Int J Chronic Obstr
- 6.6 Int J Nanomed
- 2.6 Int J Women's Health
- 2.9 Neuropsych Dis Treat
- 2.8 OncoTargets Ther
- 2.0 Patient Prefer Adher
- 2.2 Ther Clin Risk Manag
- 2.5 J Pain Res
- 3.0 Diabet Metab Synd Ob
- 3.2 Psychol Res Behav Ma
- 3.4 Nat Sci Sleep
- 1.8 Pharmgenomics Pers Med
- 2.0 Risk Manag Healthc Policy
- 4.1 J Inflamm Res
- 2.0 Int J Gen Med
- 3.4 J Hepatocell Carcinoma
- 3.0 J Asthma Allergy
- 2.2 Clin Cosmet Investig Dermatol
- 2.4 J Multidiscip Healthc
已发表论文
肝缺血再灌注损伤的新视角：cGAS-STING 通路
Authors Chen R , Yang T , Jiang Z , Long Y , Qian B, Fu W
Received 25 June 2025
Accepted for publication 3 November 2025
Published 24 November 2025 Volume 2025:18 Pages 16427—16448
DOI https://doi.org/10.2147/JIR.S549406
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 3
Editor who approved publication: Dr Fatih Türker
Runsheng Chen,1,* Tingfeng Yang,1,* Zhonghao Jiang,1 Yang Long,2 Baolin Qian,1,3 Wenguang Fu1,3
1Department of Biliary-Pancreatic Center, The Affiliated Hospital of Southwest Medical University, Luzhou, People’s Republic of China; 2Department of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Luzhou, People’s Republic of China; 3Metabolic Hepatobiliary and Pancreatic Diseases Key Laboratory of Luzhou City, Academician (Expert) Workstation of Sichuan Province, The Affiliated Hospital of Southwest Medical University, Luzhou, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Wenguang Fu, Email fuwg@swmu.edu.cn Baolin Qian, Email qianbl@swmu.edu.cn
Abstract: In hepatic ischemia-reperfusion injury (HIRI), the cGAS-STING pathway serves as a central regulatory hub by sensing aberrant mitochondrial DNA (mtDNA) release. Ischemia-reperfusion triggers mtDNA leakage through mechanisms including mitochondrial permeability transition pore (mPTP) opening, voltage-dependent anion channel (VDAC) oligomerization, and excessive fission. Cytosolic mtDNA activates cyclic GMP-AMP synthase (cGAS), catalyzing the synthesis of cGAMP, which stimulates stimulator of interferon genes (STING) oligomerization and translocation. This activates the TBK1-IRF3/NF-κB axis, driving expression of type I interferons (IFN-I) and pro-inflammatory cytokines, thereby amplifying neutrophil infiltration, macrophage pyroptosis, and hepatocyte apoptosis. The pathway bidirectionally interacts with oxidative stress and mitophagy, exhibiting cell-type specificity: in hepatocytes, cGAS promotes protective STING-independent autophagy, whereas in macrophages, STING drives inflammatory activation. Targeted inhibition of cGAS-STING signaling and mitochondrial stabilization represent promising therapeutic strategies.
Keywords: cGAS-STING pathway, hepatic ischemia/reperfusion injury, inflammatory response, oxidative stress, cell death
1Department of Biliary-Pancreatic Center, The Affiliated Hospital of Southwest Medical University, Luzhou, People’s Republic of China; 2Department of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Luzhou, People’s Republic of China; 3Metabolic Hepatobiliary and Pancreatic Diseases Key Laboratory of Luzhou City, Academician (Expert) Workstation of Sichuan Province, The Affiliated Hospital of Southwest Medical University, Luzhou, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Wenguang Fu, Email fuwg@swmu.edu.cn Baolin Qian, Email qianbl@swmu.edu.cn
Abstract: In hepatic ischemia-reperfusion injury (HIRI), the cGAS-STING pathway serves as a central regulatory hub by sensing aberrant mitochondrial DNA (mtDNA) release. Ischemia-reperfusion triggers mtDNA leakage through mechanisms including mitochondrial permeability transition pore (mPTP) opening, voltage-dependent anion channel (VDAC) oligomerization, and excessive fission. Cytosolic mtDNA activates cyclic GMP-AMP synthase (cGAS), catalyzing the synthesis of cGAMP, which stimulates stimulator of interferon genes (STING) oligomerization and translocation. This activates the TBK1-IRF3/NF-κB axis, driving expression of type I interferons (IFN-I) and pro-inflammatory cytokines, thereby amplifying neutrophil infiltration, macrophage pyroptosis, and hepatocyte apoptosis. The pathway bidirectionally interacts with oxidative stress and mitophagy, exhibiting cell-type specificity: in hepatocytes, cGAS promotes protective STING-independent autophagy, whereas in macrophages, STING drives inflammatory activation. Targeted inhibition of cGAS-STING signaling and mitochondrial stabilization represent promising therapeutic strategies.
Keywords: cGAS-STING pathway, hepatic ischemia/reperfusion injury, inflammatory response, oxidative stress, cell death