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http://purl.uniprot.org/citations/16439802http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/16439802http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/16439802http://www.w3.org/2000/01/rdf-schema#comment"Bronchial smooth muscle cell (BSMC) hyperplasia is a typical feature of airway remodeling and contributes to airway obstruction and hyperresponsiveness in asthma. Fibroblast growth factor 2 (FGF-2) and transforming growth factor beta1 (TGF-beta1) are sequentially upregulated in asthmatic airways after allergic challenge. Whereas FGF-2 induces BSMC proliferation, the mitogenic effect of TGF-beta1 remains controversial, and the effect of sequential FGF-2 and TGF-beta1 co-stimulation on BSMC proliferation is unknown. This study aimed to assess the individual and sequential cooperative effects of FGF-2 and TGF-beta1 on human BSMC proliferation and define the underlying mechanisms. Mitogenic response was measured using crystal violet staining and [3H]-thymidine incorporation. Steady-state mRNA and protein levels were measured by semiquantitative RT-PCR, Western blot, and ELISA, respectively. TGF-beta1 (0.1-20 ng/ml) alone had no effect on BSMC proliferation, but increased the proliferative effect of FGF-2 (2 ng/ml) in a concentration-dependent manner (up to 6-fold). Two distinct platelet-derived growth factor receptor (PDGFR) inhibitors, AG1296 and Inhibitor III, as well as a neutralizing Ab against PDGFRalpha, partially blocked the synergism between these two growth factors. In this regard, TGF-beta1 increased PDGF-A and PDGF-C mRNA expression as well as PDGF-AA protein expression. Moreover, FGF-2 pretreatment increased the mRNA and protein expression of PDGFRalpha and the proliferative effect of exogenous PDGF-AA (140%). Our data suggest that FGF-2 and TGF-beta1 synergize in BSMC proliferation and that this synergism is partially mediated by a PDGF loop, where FGF-2 and TGF-beta1 upregulate the receptor (PDGFRalpha) and the ligands (PDGF-AA and PDGF-CC), respectively. This powerful synergistic effect may thus contribute to the hyperplastic phenotype of BSMC in remodeled asthmatic airways."xsd:string
http://purl.uniprot.org/citations/16439802http://purl.org/dc/terms/identifier"doi:10.1165/rcmb.2005-0309oc"xsd:string
http://purl.uniprot.org/citations/16439802http://purl.org/dc/terms/identifier"doi:10.1165/rcmb.2005-0309oc"xsd:string
http://purl.uniprot.org/citations/16439802http://purl.uniprot.org/core/author"Thompson C."xsd:string
http://purl.uniprot.org/citations/16439802http://purl.uniprot.org/core/author"Thompson C."xsd:string
http://purl.uniprot.org/citations/16439802http://purl.uniprot.org/core/author"Bosse Y."xsd:string
http://purl.uniprot.org/citations/16439802http://purl.uniprot.org/core/author"Bosse Y."xsd:string
http://purl.uniprot.org/citations/16439802http://purl.uniprot.org/core/author"Rola-Pleszczynski M."xsd:string
http://purl.uniprot.org/citations/16439802http://purl.uniprot.org/core/author"Rola-Pleszczynski M."xsd:string
http://purl.uniprot.org/citations/16439802http://purl.uniprot.org/core/author"Stankova J."xsd:string
http://purl.uniprot.org/citations/16439802http://purl.uniprot.org/core/author"Stankova J."xsd:string
http://purl.uniprot.org/citations/16439802http://purl.uniprot.org/core/date"2006"xsd:gYear
http://purl.uniprot.org/citations/16439802http://purl.uniprot.org/core/date"2006"xsd:gYear
http://purl.uniprot.org/citations/16439802http://purl.uniprot.org/core/name"Am. J. Respir. Cell Mol. Biol."xsd:string
http://purl.uniprot.org/citations/16439802http://purl.uniprot.org/core/name"Am. J. Respir. Cell Mol. Biol."xsd:string
http://purl.uniprot.org/citations/16439802http://purl.uniprot.org/core/pages"746-753"xsd:string
http://purl.uniprot.org/citations/16439802http://purl.uniprot.org/core/pages"746-753"xsd:string
http://purl.uniprot.org/citations/16439802http://purl.uniprot.org/core/title"Fibroblast growth factor 2 and transforming growth factor beta1 synergism in human bronchial smooth muscle cell proliferation."xsd:string
http://purl.uniprot.org/citations/16439802http://purl.uniprot.org/core/title"Fibroblast growth factor 2 and transforming growth factor beta1 synergism in human bronchial smooth muscle cell proliferation."xsd:string
http://purl.uniprot.org/citations/16439802http://purl.uniprot.org/core/volume"34"xsd:string
http://purl.uniprot.org/citations/16439802http://purl.uniprot.org/core/volume"34"xsd:string
http://purl.uniprot.org/citations/16439802http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/16439802
http://purl.uniprot.org/citations/16439802http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/16439802
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