Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2001-8-8
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0959-9673
pubmed:author
pubmed:issnType
Print
pubmed:volume
82
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
231-41
pubmed:dateRevised
2004-11-17
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
pubmed:year
2001
pubmed:articleTitle
Peplomycin, a bleomycin derivative, induces myofibroblasts in pulmonary fibrosis.
pubmed:affiliation
Department of Oral Surgery, Kochi Medical School, Kochi, Japan.
pubmed:publicationType
Journal Article