title: Smad3 deficiency attenuates bleomycin-induced pulmonary fibrosis in mice.
abstract: Transforming growth factor-beta (TGF-beta) signaling plays an important regulatory role during lung fibrogenesis. Smad3 was identified in the pathway for transducing TGF-beta signals from the cell membrane to the nucleus. Using mice without Smad3 gene expression, we investigated whether Smad3 could regulate bleomycin-induced pulmonary fibrosis in vivo. Mice deficient in Smad3 demonstrated suppressed type I procollagen mRNA expression and reduced hydroxyproline content in the lungs compared with wild-type mice treated with bleomycin. Furthermore, loss of Smad3 greatly attenuated morphological fibrotic responses to bleomycin in the mouse lungs, suggesting that Smad3 is implicated in the pathogenesis of pulmonary fibrosis. These results show that Smad3 contributes to bleomycin-induced lung injury and that Smad3 may serve as a novel target for potential therapeutic treatment of lung fibrosis.
authors.affiliation: Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, California 90033, USA. jingsongzhao@yahoo.com
authors.forename: Jingsong
authors.initials: J
authors.lastname: Zhao
authors.forename: Wei
authors.initials: W
authors.lastname: Shi
authors.forename: Yan-Ling
authors.initials: YL
authors.lastname: Wang
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.forename: Pablo
authors.initials: P
authors.lastname: Bringas
authors.forename: Michael B
authors.initials: MB
authors.lastname: Datto
authors.forename: Joshua P
authors.initials: JP
authors.lastname: Frederick
authors.forename: Xiao-Fan
authors.initials: XF
authors.lastname: Wang
authors.forename: David
authors.initials: D
authors.lastname: Warburton
mesh_terms: D000818:Animals; D001761:Bleomycin; D003094:Collagen / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000172:deficiency* / Q000235:genetics; D005353:Fibronectins / Q000378:metabolism; D008168:Lung / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D011658:Pulmonary Fibrosis / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology*; D051900:Smad3 Protein; D015534:Trans-Activators / Q000172:deficiency* / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; D005353:Fibronectins; D051900:Smad3 Protein; C497791:Smad3 protein, mouse; D015534:Trans-Activators; D001761:Bleomycin; D003094:Collagen