GAMG alleviates silicosis inflammation and fibrosis by targeting STING

  • Ecotoxicol Environ Saf. 2026 Aug:321:120405. doi: 10.1016/j.ecoenv.2026.120405.
Jing Zhang  1 ,  Miaoqing Xiang  2 ,  Zongze Yao  3 ,  Wei Shao  3 ,  Zhiyu Liu  4 ,  Wenjian Tang  5 ,  Xinrong Tao  6 ,  Biyong Liu  7
Affiliations
  • 1. School of Public Health, Anhui University of Science and Technology, Hefei, Anhui 231131, China; Anhui Province Key Laboratory of Occupational Health, Anhui No.2 Provincial People's Hospital, Hefei 230041, China; Joint Research Center for Occupational Medicine and Health of IHM, Anhui University of Science and Technology, Huainan 232000, China. Electronic address: [email protected].
  • 2. School of Public Health, Anhui University of Science and Technology, Hefei, Anhui 231131, China.
  • 3. Anhui Province Key Laboratory of Occupational Health, Anhui No.2 Provincial People's Hospital, Hefei 230041, China.
  • 4. School of Pharmacy, Anhui Medical University, Hefei 230032, China.
  • 5. Anhui Province Key Laboratory of Occupational Health, Anhui No.2 Provincial People's Hospital, Hefei 230041, China; School of Pharmacy, Anhui Medical University, Hefei 230032, China. Electronic address: [email protected].
  • 6. School of Public Health, Anhui University of Science and Technology, Hefei, Anhui 231131, China. Electronic address: [email protected].
  • 7. Anhui Province Key Laboratory of Occupational Health, Anhui No.2 Provincial People's Hospital, Hefei 230041, China. Electronic address: [email protected].
PMID: 42341724 DOI: 10.1016/j.ecoenv.2026.120405
Abstract

Silicosis is a severe occupational lung disease characterized by persistent inflammation and progressive fibrosis with no effective treatment. Glycyrrhetinic acid-3-O-β-D-glucuronide (GAMG), an active metabolite of glycyrrhizin, has anti-inflammatory and anti-fibrotic efficacy in our previous work, but its direct molecular target remains unknown. Through integrated multi-omics and molecular docking, we identified stimulator of interferon genes (STING) as a key pathogenic driver and a potential target of GAMG in silica-induced pulmonary injury. In silicosis patients, levels of dsDNA, STING, HMGB1, and α-SMA were significantly elevated (P < 0.01) and correlated with disease severity. Surface plasmon resonance (SPR) showed that GAMG directly binds to STING (Kd = 11.44 µM). Cellular thermal shift assays (CETSA) further demonstrated that GAMG enhances STING stability. In MH-S Macrophages, GAMG inhibited the STING/TBK1/NF-κB pathway and reduced silica-induced release of pro-inflammatory (IL-6 and TNF-α) and pro-fibrotic cytokine TGF-β1. In a murine silicosis model, GAMG (100 mg/kg) treatment reduced dsDNA accumulation and blocked STING activation. Moreover, GAMG alleviated lung inflammation and Collagen deposition. Collectively, these findings revealed that GAMG targeted the STING/TBK1/NF-κB pathway to alleviate silicosis, identifying STING as a potential therapeutic target. This work supported GAMG as a promising natural metabolite for treating silica-induced lung injury.

Keywords
Fibrosis; GAMG; Inflammation; Natural product; STING; Silicosis.
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