Temporal expression and cellular distribution of pulmonary fibronectin gene induction following exposure to an...

This study examines the ability of an emission source particle, residual oil fly ash (ROFA), to influence pulmonary fibronectin (Fn) gene expression. Fn is an extracellular matrix (ECM) protein involved in a variety of cellular functions, including inflammation, cell proliferation, and fibrosis. Temporal expression and spatial distribution of Fn gene induction were assessed by in situ hybridization in rat lung during acute phase of lung injury occurring 6 to 72 h following intratracheal instillation of ROFA. Fn mRNA was not detected in rat lungs treated with either saline or at 6 h after ROFA treatment. However, Fn mRNA was induced in airway epithelial cells 24 h after ROFA instillation. Histopathology showed peribronchial inflammation and focal edema. Diffuse inflammation in alveolar region with limited expression of Fn mRNA was evident 48 h after ROFA exposure, occurring mainly in proliferating epithelial cells. Extensive Fn mRNA expression was seen in proliferating fibroblasts and in hyperplastic epithelial cells within incipient fibrotic lesions 72 h after exposure, while the intensity of expression in the airway epithelial cells was decreased. Therefore, Fn mRNA induction was associated with inflammatory and incipient fibrotic lesions, indicating its possible involvement in airway hyperreactivity and initiation of fibrogenesis.