A peptide derived from endostatin ameliorates organ fibrosis.
A peptide derived from endostatin ameliorates organ fibrosis.
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DOI：
10.1126/scitranslmed.3003421
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发表时间：
2012-05-30
影响因子：
17.1
通讯作者：
Feghali-Bostwick CA
中科院分区：
文献类型：
--
作者：
Yamaguchi Y;Takihara T;Chambers RA;Veraldi KL;Larregina AT;Feghali-Bostwick CA
纤维增生性疾病，如特发性肺纤维化和系统性硬化症没有有效的治疗方法，并且由于进行性器官纤维化导致显著的发病率和死亡率。我们在体外、离体和体内研究了内皮抑素衍生的肽对人类和小鼠组织中现有纤维化和由两种有效介质——转化生长因子-β (TGF-β)和博来霉素引发的纤维化的影响。我们发现一种肽E4具有有效的抗纤维化活性。E4在体内小鼠模型、体外人皮肤、博莱霉素诱导的皮肤和肺纤维化中均能抑制TGF-β诱导的真皮纤维化，表明E4具有较强的抗纤维化作用。此外，在这些临床前模型中，E4显著减少了现有的纤维化。E4纤维化的改善伴随着细胞凋亡的减少和赖氨酸氧化酶水平的降低，赖氨酸氧化酶是一种交联胶原的酶，Egr-1（早期生长反应基因-1）是一种介导几种纤维化触发因素的转录因子。我们的研究结果确定E4是一种具有有效抗纤维化活性的肽，可能是器官纤维化的治疗剂。
Fibroproliferative disorders such as idiopathic pulmonary fibrosis and systemic sclerosis have no effective therapies and result in significant morbidity and mortality due to progressive organ fibrosis. We examined the effect of peptides derived from endostatin on existing fibrosis and fibrosis triggered by two potent mediators, transforming growth factor–β (TGF-β) and bleomycin, in human and mouse tissues in vitro, ex vivo, and in vivo. We identified one peptide, E4, with potent antifibrotic activity. E4 prevented TGF-β–induced dermal fibrosis in vivo in a mouse model, ex vivo in human skin, and in bleomycin-induced dermal and pulmonary fibrosis in vivo, demonstrating that E4 exerts potent antifibrotic effects. In addition, E4 significantly reduced existing fibrosis in these preclinical models. E4 amelioration of fibrosis was accompanied by reduced cell apoptosis and lower levels of lysyl oxidase, an enzyme that cross-links collagen, and Egr-1 (early growth response gene–1), a transcription factor that mediates the effects of several fibrotic triggers. Our findings identify E4 as a peptide with potent antifibrotic activity and a possible therapeutic agent for organ fibrosis.
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影响因子：
6
作者：
Pilewski, JM;Liu, LX;Feghali-Bostwick, CA
通讯作者：
Feghali-Bostwick, CA
影响因子：
4.8
作者：
Kim, YM;Hwang, S;Kwon, YG
通讯作者：
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影响因子：
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作者：
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影响因子：
10
作者：
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通讯作者：
Thickett, D. R.
影响因子：
3.7
作者：
Cattaneo, MG;Pola, S;Vicentini, LM
通讯作者：
Vicentini, LM