Source:http://linkedlifedata.com/resource/pubmed/id/11493347
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
4
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pubmed:dateCreated |
2001-8-8
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pubmed:abstractText |
To analyse the mechanism by which a bleomycin derivative, peplomycin (PLM) induces pulmonary fibrosis, we investigated differentiation of rat pulmonary fibroblasts to myofibroblasts (MF). In intraperitoneally PLM (5 mg/kg/day)-injected rats, the peripheries of lungs adjacent to the pleura revealed advanced fibrosis with a small number of alpha-smooth muscle actin (alpha-SMA)-positive MF, which ultrastructurally possessed abundant microfilaments and cellular organelles. In the fibrotic tissue, the expression of alpha-SMA-mRNA was detected by in situ reverse transcription-polymerase (RT-PCR). The message was strong just after a 2-week administration of PLM then decreased thereafter, although fibrosis advanced. When pulmonary fibroblasts were separated from saline-injected rats (N-Fib) and cultivated for 7 days in the presence of 5 mg/mL PLM, alpha-SMA protein was weakly expressed, while the majority of pulmonary fibroblasts separated from PLM-injected rats (P-Fib) became positive for alpha-SMA in 7-day cultivation and the expression of alpha-SMA in P-Fib was strongly increased by cultivation in the presence of PLM and transforming growth factor-beta (TGF-beta), but not basic fibroblast growth factor (bFGF) or platelet-derived growth factor (PDGF), although the cell proliferation was most strongly enhanced by bFGF and only slightly by PLM and TGF-beta. The alpha-SMA-positive cells expressed vimentin, but only weakly expressed desmin. Additionally, P-Fib generated larger amounts of TGF-beta and bFGF than were generated by N-Fib. These results indicate that PLM induces pulmonary fibrosis by differentiating fibroblasts to alpha-SMA-positive MF, and that bFGF and TGF-beta play each critical role in the different phases of PLM-induced pulmonary fibrosis by inducing fibroblast proliferation and transformation, respectively.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Actins,
http://linkedlifedata.com/resource/pubmed/chemical/Antibiotics, Antineoplastic,
http://linkedlifedata.com/resource/pubmed/chemical/Fibroblast Growth Factor 2,
http://linkedlifedata.com/resource/pubmed/chemical/Peplomycin,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0959-9673
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
82
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
231-41
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pubmed:dateRevised |
2004-11-17
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pubmed:meshHeading |
pubmed-meshheading:11493347-Actins,
pubmed-meshheading:11493347-Animals,
pubmed-meshheading:11493347-Antibiotics, Antineoplastic,
pubmed-meshheading:11493347-Blotting, Northern,
pubmed-meshheading:11493347-Blotting, Western,
pubmed-meshheading:11493347-Cell Culture Techniques,
pubmed-meshheading:11493347-Cell Differentiation,
pubmed-meshheading:11493347-Cell Division,
pubmed-meshheading:11493347-Fibroblast Growth Factor 2,
pubmed-meshheading:11493347-Fibroblasts,
pubmed-meshheading:11493347-Gene Expression Regulation,
pubmed-meshheading:11493347-Male,
pubmed-meshheading:11493347-Peplomycin,
pubmed-meshheading:11493347-Pulmonary Fibrosis,
pubmed-meshheading:11493347-RNA, Messenger,
pubmed-meshheading:11493347-Rats,
pubmed-meshheading:11493347-Rats, Inbred F344,
pubmed-meshheading:11493347-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:11493347-Transforming Growth Factor beta
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pubmed:year |
2001
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pubmed:articleTitle |
Peplomycin, a bleomycin derivative, induces myofibroblasts in pulmonary fibrosis.
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pubmed:affiliation |
Department of Oral Surgery, Kochi Medical School, Kochi, Japan.
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pubmed:publicationType |
Journal Article
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