Sorafenib ameliorates bleomycin-induced pulmonary fibrosis: potential roles in the inhibition of epithelial-mesenchymal transition and fibroblast activation.
Sorafenib ameliorates bleomycin-induced pulmonary fibrosis: potential roles in the inhibition of epithelial-mesenchymal transition and fibroblast activation.
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DOI：
10.1038/cddis.2013.154
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发表时间：
2013-06-13
影响因子：
9
通讯作者：
Ding, X.
中科院分区：
文献类型：
--
作者：
Chen, Y-L;Zhang, X.;Bai, J.;Gai, L.;Ye, X-L;Zhang, L.;Xu, Q.;Zhang, Y-X;Xu, L.;Li, H-P;Ding, X.
特发性肺纤维化（IPF）是一种严重的进行性和不可逆的肺部疾病，病因不明，治疗选择很少。这种疾病曾被认为是一种慢性炎症驱动的过程，但越来越多的人认识到，上皮-间质转化（EMT）有助于响应损伤的成纤维细胞积累的细胞起源。在肺纤维化疾病的发病机制中，转化生长因子-β（TGF-β）信号传导被认为是EMT和成纤维细胞活化的关键诱导剂，并且已经开发了许多干扰TGF-β信号传导的治疗干预以逆转已建立的纤维化。然而，目前还没有有效且耐受性良好的抗纤维化药物。先前，我们报道了索拉非尼在体外拮抗小鼠肝细胞中TGF-β信号传导的鉴定。在本文中，我们继续评估索拉非尼对博莱霉素（BLM）诱导的小鼠肺纤维化的抗纤维化作用。我们进一步证明索拉非尼不仅能显著抑制TGF-β1诱导的肺泡上皮细胞EMT，而且能同时抑制成纤维细胞的增殖和胶原合成。此外，我们提供了体内证据，表明索拉非尼抑制小鼠中BLM介导的EMT和成纤维细胞活化的症状，证实了该药物对IPF患者的治疗潜力。
Idiopathic pulmonary fibrosis (IPF) is a serious progressive and irreversible lung disease with unknown etiology and few treatment options. This disease was once thought to be a chronic inflammatory-driven process, but it is increasingly recognized that the epithelial–mesenchymal transition (EMT) contributes to the cellular origin of fibroblast accumulation in response to injury. During the pathogenesis of pulmonary fibrotic diseases, transforming growth factor-β (TGF-β) signaling is considered a pivotal inducer of EMT and fibroblast activation, and a number of therapeutic interventions that interfere with TGF-β signaling have been developed to reverse established fibrosis. However, efficient and well-tolerated antifibrotic agents are not currently available. Previously, we reported the identification of sorafenib to antagonize TGF-β signaling in mouse hepatocytes in vitro. In this manuscript, we continued to evaluate the antifibrotic effects of sorafenib on bleomycin (BLM)-induced pulmonary fibrosis in mice. We further demonstrated that sorafenib not only profoundly inhibited TGF-β1-induced EMT in alveolar epithelial cells, but also simultaneously reduced the proliferation and collagen synthesis in fibroblasts. Additionally, we presented in vivo evidence that sorafenib inhibited the symptoms of BLM-mediated EMT and fibroblast activation in mice, warranting the therapeutic potential of this drug for patients with IPF.
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影响因子：
2.9
作者：
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通讯作者：
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DOI：
10.1164/rccm.200906-0964oc
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发表时间：
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影响因子：
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