| pubmed-article:11493347 | 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. | lld:pubmed |
