2. Academic Validation
  3. Fibrinogen Gamma Chain Mediates Airway Inflammation and Remodeling Through the Focal Adhesion and TGF-β/Smad2 Pathways in Chronic Obstructive Pulmonary Disease

Fibrinogen Gamma Chain Mediates Airway Inflammation and Remodeling Through the Focal Adhesion and TGF-β/Smad2 Pathways in Chronic Obstructive Pulmonary Disease

  • Lung. 2025 Nov 19;203(1):100. doi: 10.1007/s00408-025-00856-w.
Jiali Weng 1,  Hai Zhang 1 2,  Qing Chang 1,  Yi Feng 1,  Meiqin Xie 1,  Chenfei Li 1,  Qi Liu 1,  Xiaohui Wang 1,  Mengnan Li 1,  Yuqing Chen 1,  Chunhua Ling 2,  Kai Wang 3,  Xiaohua Yang 3,  Feng Li 4
Affiliations

Affiliations

  • 1 Department of Pulmonary and Critical Care Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, NO.241, West Huaihai Road, Shanghai, 200030, People's Republic of China.
  • 2 Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Soochow University, Suzhou, 215000, People's Republic of China.
  • 3 Department of Central Laboratory, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200030, People's Republic of China.
  • 4 Department of Pulmonary and Critical Care Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, NO.241, West Huaihai Road, Shanghai, 200030, People's Republic of China. [email protected].
PMID: 41254304 DOI: 10.1007/s00408-025-00856-w
Abstract

Background: Chronic obstructive pulmonary disease (COPD) is a progressive disease characterized by chronic airway inflammation and remodeling. Fibrinogen gamma chain (FGG) has been implicated in the pathogenesis of multiple inflammatory and fibrotic conditions. However, the role and mechanisms of FGG in COPD remain unclear.

Methods: FGG expression in lung tissues and plasma of COPD patients and CS-exposed mice was assessed. To investigate its functional role in cigarette smoke extract (CSE)-induced inflammation and epithelial-mesenchymal transition (EMT), we employed FGG knockdown (KD) and recombinant human FGG (rFGG) protein treatment in BEAS-2B cells and in a murine COPD model. To elucidate the related mechanisms in CSE-induced airway inflammation and EMT, BEAS-2B cells were treated with PF573228 (10 µM, a FAK Inhibitor) or SB431542 (10 µM, a TGF-β type I receptor inhibitor).

Results: FGG was up-regulated in both the lung tissue and plasma of COPD patients. Plasma FGG levels were negatively correlated with lung function in COPD patients. Similarly, elevated FGG expression was verified in CS-exposed mice and CSE-induced BEAS-2B cells. Both in vitro (FGG-KD in BEAS-2B) and in vivo (mouse model) experiments demonstrated that inhibition of FGG expression attenuated CSE-induced inflammatory cytokine release and EMT. Treatment with PF573228 or SB431542 inhibited airway inflammation and EMT, implicating the focal adhesion and TGF-β/SMAD2 pathways.

Conclusions: FGG contributes to airway inflammation and remodeling in COPD. Cigarette smoke enhances FGG expression and secretion in bronchial epithelium. Increased FGG promotes the release of inflammatory cytokines and EMT through the focal adhesion and TGF-β/SMAD2 pathways.

Keywords

Airway epithelium inflammation; Chronic obstructive pulmonary disease; Epithelial-mesenchymal transition; Fibrinogen gamma chain.

Figures
Products