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An essential role for CCAAT/enhancer binding protein β in bleomycin‐induced pulmonary fibrosis
Author(s) -
Hu B,
Ullenbruch MR,
Jin H,
GharaeeKermani M,
Phan SH
Publication year - 2007
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.2119
Subject(s) - myofibroblast , bleomycin , pulmonary fibrosis , fibrosis , ccaat enhancer binding proteins , lung , cytokine , pathology , biology , pathogenesis , medicine , cancer research , transcription factor , immunology , nuclear protein , gene , biochemistry , chemotherapy
Pulmonary fibrosis is characterized by inflammation, genesis of myofibroblasts, and abnormal tissue repair. Despite extensive research, its pathogenesis remains incompletely understood. Previously, the transcription factor CCAAT/enhancer binding protein β (C/EBPβ) was found to be a key regulator of myofibroblast differentiation in vitro , and to be involved in the acute phase and inflammatory responses. In an attempt to test the role of C/EBPβ in the development of pulmonary fibrosis, experiments using C/EBP β null mice and their wild‐type littermates were conducted. Our findings indicated that, compared to wild‐type mice, animals deficient in C/EBPβ showed significantly reduced fibrotic lesions and collagen deposition in the lung upon endotracheal injection of bleomycin. Further studies on the mechanisms by which C/EBPβ regulates fibrosis indicated that knockout of C/EBP β attenuates inflammatory cytokine expression in bleomycin‐treated mice. The reduced α‐smooth muscle actin gene expression in either isolated lung fibroblasts or lung tissue from bleomycin or saline‐treated C/EBPβ deficient mice suggests that C/EBPβ regulates myofibroblast differentiation during fibrosis. Consistent with this finding, cells from C/EBPβ deficient mice exhibited higher proliferative rates than those from wild‐type mice. These data suggest that C/EBPβ plays an essential role in pulmonary fibrosis and that this role appears to be multifactorial with respect to cytokine expression, cell differentiation, and proliferation. Copyright © 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.