Pirfenidone inhibits PDGF isoforms in bleomycin hamster model of lung fibrosis at the translational level
Pirfenidone inhibits PDGF isoforms in bleomycin hamster model of lung fibrosis at the translational level
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DOI：
10.1152/ajplung.1999.276.2.l311
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发表时间：
1999-02-01
影响因子：
4.9
通讯作者：
Giri, SN
中科院分区：
文献类型：
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作者：
Gurujeyalakshmi, G;Hollinger, MA;Giri, SN
吡非尼酮（PD）因其在肺纤维化的博来霉素（BL）仓鼠模型中的抗纤维化作用而闻名。我们评估了在相同的肺纤维化模型中，用PD预处理仓鼠是否可以影响BL诱导的血小板衍生生长因子（PDGF）-A和PDGF-B基因和蛋白的过表达的效果。我们通过RT-PCR分析证明，与盐水对照仓鼠相比，BL处理的肺的支气管肺泡灌洗（BAL）细胞中PDGF-A和PDGF-B mRNA水平升高。然而，这些水平没有改变BAL细胞从BL处理的仓鼠饮食含有0.5%的PD。BALF液中PDGF亚型的Western印迹分析表明，PD治疗抑制了PDGF-A和PDGF-B亚型的合成。PD处理还降低了BL处理的仓鼠肺的BAL液中的促有丝分裂活性。综上所述，这些数据提供了证据表明，PD对BL诱导的肺纤维化的保护作用可能是通过减少肺巨噬细胞产生的PDGF亚型介导的。
Pirfenidone (PD) is known for its antifibrotic effects in the bleomycin (BL) hamster model of lung fibrosis. We evaluated whether pretreatment of hamsters with PD could influence the effects of BL-induced overexpression of platelet-derived growth factor (PDGF)-A and PDGF-B genes and proteins in the same model of lung fibrosis. We demonstrate elevated levels of PDGF-A and PDGF-B mRNAs in bronchoalveolar lavage (BAL) cells from lungs of BL-treated compared with saline control hamsters by RT-PCR analysis. However, these levels were not altered in BAL cells obtained from BL-treated hamsters on diets containing 0.5% PD. Western blot analysis of BAL fluid for PDGF isoforms demonstrated that PD treatment inhibited the synthesis of both PDGF-A and PDGF-B isoforms. PD treatment also decreased the mitogenic activity in the BAL fluid from BL-treated hamster lungs. Taken together, these data provide evidence that the protective effects of PD against BL-induced lung fibrosis may be mediated by a reduction in PDGF isoforms produced by lung macrophages.