Tissue Factor Driven Coagulation and Inflammation in Lung Injury: Insights From In Vitro and In Vivo Models

Area of Science:

• Pulmonary Medicine and Pathology
• Hematology and Coagulation
• Molecular Biology and Immunology

Background:

• Lung injury and fibrosis involve complex interactions between inflammation and coagulation.
• Tissue factor (TF) initiates the extrinsic coagulation cascade, but its role in lung fibrin deposition is not fully understood.
• Pulmonary fibrosis (PF) progression is linked to dysregulated coagulation pathways.

Purpose of the Study:

• To investigate the role of TF in mediating coagulation-driven inflammation and fibrin deposition in lung injury.
• To elucidate TF-mediated molecular mechanisms contributing to pulmonary fibrosis.
• To explore potential therapeutic targets for mitigating TF-driven lung pathology.

Main Methods:

• Utilized in vitro (A549, Beas2b cells) and in vivo (C57BL/6 mice) models with bleomycin (BLM), TGF-β, and TF.
• Integrated protein-protein interaction (PPI) network and gene enrichment analyses.
• Performed gene expression analysis, immunofluorescence, and histological assessments (H&E, Masson Trichrome).

Main Results:

• Increased expression of coagulation factors (CF-III, CF-VII, CF-X) in lung epithelial cells, with heightened pro-coagulant activity in A549 cells.
• Elevated inflammatory cytokines (IL-6, TNF-α, IL-1β) and marked TF and TNF-α upregulation observed.
• Histological analysis confirmed inflammatory and fibrotic changes in murine lung tissues, correlating with TF activity.

Conclusions:

• Tissue factor (TF) is a key molecular driver of thrombo-inflammatory lung injury and pulmonary fibrosis.
• TF mediates inflammation, fibrin deposition, endothelial dysfunction, and fibrotic remodeling.
• Targeting TF presents a potential therapeutic strategy for treating lung injury and fibrosis.