The role of cGAS-STING signaling in pulmonary fibrosis and its therapeutic potential

Jing Zhang; Lanlan Zhang; Yutian Chen; Xiaobin Fang; Bo Li; Chunheng Mo

doi:10.3389/fimmu.2023.1273248

The role of cGAS-STING signaling in pulmonary fibrosis and its therapeutic potential

Front Immunol. 2023 Oct 25:14:1273248. doi: 10.3389/fimmu.2023.1273248. eCollection 2023.

Authors

Jing Zhang^#^{1

2}, Lanlan Zhang^#³, Yutian Chen⁴, Xiaobin Fang⁵, Bo Li⁶, Chunheng Mo¹

Affiliations

¹ Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, State Key Laboratory of Biotherapy, West China Second University Hospital, Sichuan University, Chengdu, China.
² School of Basic Medicine, Jining Medical University, Jining, Shandong, China.
³ State Key Laboratory of Respiratory Health and Multimorbidity, Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, China.
⁴ The Department of Endovascular Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
⁵ Fujian Provincial Key Laboratory of Critical Care Medicine, Department of Anesthesiology/Critical Care Medicine, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou, China.
⁶ Department of Radiology, West China Hospital, Sichuan University, Chengdu, China.

^# Contributed equally.

Abstract

Pulmonary fibrosis is a progressive and ultimately fatal lung disease, exhibiting the excessive production of extracellular matrix and aberrant activation of fibroblast. While Pirfenidone and Nintedanib are FDA-approved drugs that can slow down the progression of pulmonary fibrosis, they are unable to reverse the disease. Therefore, there is an urgent demand to develop more efficient therapeutic approaches for pulmonary fibrosis. The intracellular DNA sensor called cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) synthase (cGAS) plays a crucial role in detecting DNA and generating cGAMP, a second messenger. Subsequently, cGAMP triggers the activation of stimulator of interferon genes (STING), initiating a signaling cascade that leads to the stimulation of type I interferons and other signaling molecules involved in immune responses. Recent studies have highlighted the involvement of aberrant activation of cGAS-STING contributes to fibrotic lung diseases. This review aims to provide a comprehensive summary of the current knowledge regarding the role of cGAS-STING pathway in pulmonary fibrosis. Moreover, we discuss the potential therapeutic implications of targeting the cGAS-STING pathway, including the utilization of inhibitors of cGAS and STING.

Keywords: cGAS-STING; inhibitors; pulmonary fibrosis; signaling pathway; therapeutic potential.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Chromogranin A
DNA
Humans
Nucleotidyltransferases
Pulmonary Fibrosis* / drug therapy
Pulmonary Fibrosis* / etiology
Second Messenger Systems
Signal Transduction

Substances

Chromogranin A
DNA
Nucleotidyltransferases
cGAS protein, human
STING1 protein, human

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the National Natural Science Foundation of China (82200084), Natural Science Foundation of Sichuan Province (2023NSFSC1456), the Fundamental Research Funds for the Central Universities, Postdoctoral Science Foundation funded project of Sichuan Province (TB2023047), and Sichuan University postdoctoral interdisciplinary Innovation Fund (0020404153020).