Myofibroblasts and their role in lung collagen gene expression during pulmonary fibrosis. A combined immunohistochemical and in situ hybridization study.
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.
Zhang
K
K
Department of Pathology, University of Michigan, Ann Arbor 48109-060.
Rekhter
M D
MD
Gordon
D
D
Phan
S H
SH
D000199:Actins / Q000032:analysis*; D000818:Animals; D001483:Base Sequence; D001761:Bleomycin; D003893:Desmin / Q000032:analysis*; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000737:chemistry*; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008168:Lung / Q000737:chemistry / Q000473:pathology*; D008297:Male; D008969:Molecular Sequence Data; D011347:Procollagen / Q000032:analysis* / Q000235:genetics; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000473:pathology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011916:Rats, Inbred F344; D013047:Specific Pathogen-Free Organisms; D013997:Time Factors
D000199:Actins; D003893:Desmin; D011347:Procollagen; D012333:RNA, Messenger; D001761:Bleomycin