Myofibroblasts and their role in lung collagen gene expression during pulmonary fibrosis. A combined immunohistochemical and in situ hybridization study.

K Zhang, MD Rekhter, D Gordon… - The American journal of …, 1994 - ncbi.nlm.nih.gov
K Zhang, MD Rekhter, D Gordon, SH Phan
The American journal of pathology, 1994ncbi.nlm.nih.gov
Appearance of contractile filament-laden stromal cells or myofibroblasts is a characteristic of
lung fibrotic lesions. The role of these cells in fibrosis and their cytoskeletal phenotype are
not fully delineated. This study was undertaken to further investigate these issues using a
model of lung fibrosis. Rats were treated endotracheally with bleomycin on day 0, and their
lungs examined at various time points by in situ hybridization for alpha 1 (I) procollagen
mRNA expression and by immunohistochemistry for desmin and alpha-smooth muscle actin …
Abstract
Appearance of contractile filament-laden stromal cells or myofibroblasts is a characteristic of lung fibrotic lesions. The role of these cells in fibrosis and their cytoskeletal phenotype are not fully delineated. This study was undertaken to further investigate these issues using a model of lung fibrosis. Rats were treated endotracheally with bleomycin on day 0, and their lungs examined at various time points by in situ hybridization for alpha 1 (I) procollagen mRNA expression and by immunohistochemistry for desmin and alpha-smooth muscle actin expression. The results show an increase in the number of cells resembling fibroblasts and strongly positive for alpha-smooth muscle actin, desmin and procollagen mRNA expression in lungs of animals treated with bleomycin, with the increase being maximal between days 7 and 14 after bleomycin treatment. Two types of newly positive cells could be discerned. The first expressing alpha-smooth muscle actin, desmin, and procollagen mRNA was localized in active fibrotic lesions. The second expressing only alpha-smooth muscle actin and procollagen mRNA was localized in fibrotic submesothelial areas. Almost all of the newly reactive alpha-smooth muscle actin-positive cells strongly express procollagen mRNA, and they constituted most of the cells actively expressing procollagen. These findings suggest that the newly appearing myofibroblast characterized by alpha-smooth muscle actin and/or desmin expression may be responsible for most if not all of the increased lung collagen gene expression in pulmonary fibrosis.
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