RRC ID 69610
Author Usuki J, Matsuda K, Azuma A, Kudoh S, Gemma A.
Title Sequential analysis of myofibroblast differentiation and transforming growth factor-β1/Smad pathway activation in murine pulmonary fibrosis.
Journal J Nippon Med Sch
Abstract Myofibroblasts play a critical role in tissue fibrosis. However, the intracellular signaling pathways in myofibroblast differentiation are poorly understood. Here, we studied the relationship between transforming growth factor-β (TGF-β)/Smad pathway activation and myofibroblast differentiation in both in vivo and in vitro experiments. In murine bleomycin-induced pulmonary fibrosis, nuclear localization of phosphorylated Smad2/3 (p-Smad2/3) was observed in pulmonary fibrotic lesions 7 days after bleomycin injection, whereas α-smooth muscle actin (ASMA)-positive myofibroblasts appeared in the lesions at 14 days, when the cytoplasmic localization of p-Smad2/3 was observed. We also compared the effects of TGF-β1 on myofibroblast differentiation and on type I collagen expression in a murine lung fibroblast cell line (MLg2908). TGF-β1 induced rapid expression of p-Smad2/3 in nuclei, after which ASMA organization in the cytoplasm of fibroblasts was observed. However, TGF-β1 produced no effect on the quantity of ASMA, either in mRNA levels or protein levels, even after the phosphorylation of Smad2/3. In contrast, TGF-β1 upregulated the expression of type I collagen mRNA. These findings suggest that in pulmonary fibrosis the molecular mechanism of myofibroblast differentiation is complex and that the difference between ASMA expression and type I collagen expression is mediated by the TGF-β/Smad pathway.
Volume 79(1)
Pages 46-59
Published 2012-1-1
DOI 10.1272/jnms.79.46
PII JST.JSTAGE/jnms/79.46
PMID 22398790
MeSH 3T3 Cells Actins / genetics Actins / metabolism Animals Bleomycin Cell Differentiation* / drug effects Collagen Type I / genetics Collagen Type I / metabolism Gene Expression Regulation / drug effects Humans Immunohistochemistry Lung / drug effects Lung / metabolism Lung / pathology Male Mice Mice, Inbred C57BL Myofibroblasts / drug effects Myofibroblasts / metabolism* Myofibroblasts / pathology* Pulmonary Fibrosis / genetics Pulmonary Fibrosis / pathology* RNA, Messenger / genetics RNA, Messenger / metabolism Signal Transduction* / drug effects Smad Proteins / genetics Smad Proteins / metabolism* Time Factors Transforming Growth Factor beta1 / metabolism* Transforming Growth Factor beta1 / pharmacology
IF 0.826
Human and Animal Cells 3T3