Early growth response gene 1-mediated apoptosis is essential for transforming growth factor beta1-induced pulmonary fibrosis.
Early growth response gene 1-mediated apoptosis is essential for transforming growth factor beta1-induced pulmonary fibrosis.
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早期生长反应基因1介导的凋亡对于转化生长因子beta1诱导的肺纤维化至关重要。
DOI：
10.1084/jem.20040104
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发表时间：
2004-08-02
影响因子：
15.3
通讯作者：
Elias, JA
中科院分区：
文献类型：
--
作者：
Lee, CG;Cho, SJ;Kang, MJ;Chapoval, SR;Lee, PJ;Noble, PW;Yehualaeshet, T;Lu, BF;Flavell, RA;Milbrandt, J;Homer, RJ;Elias, JA
在肺疾病如哮喘和间质性疾病中，纤维化和细胞凋亡并置，并且转化生长因子（TGF）-β1已经涉及这些反应的发病机制。然而，TGF-β1在肺中的体内效应器功能及其在这些反应的发病机制中的作用尚未完全了解。此外，细胞凋亡和其他TGF-β1诱导的反应之间的关系尚未确定。为了解决这些问题，我们使用一种新的外部可调节的三重转基因系统将生物活性TGF-β1靶向小鼠肺。TGF-β1引起短暂的上皮细胞凋亡，随后出现单核细胞丰富的炎症、组织纤维化、肌成纤维细胞和肌细胞增生以及房间隔破裂伴蜂窝样改变。对这些小鼠的研究强调了这种纤维化反应的可逆性。他们还证明，早期生长反应基因（Egr）-1的无效突变或半胱天冬酶抑制剂阻断了TGF-β1诱导的细胞凋亡。有趣的是，这两种干预措施都显着改善TGF-β1诱导的纤维化和肺泡重塑。这些研究阐明了TGF-β1在体内的复杂作用，并确定了Egr-1在TGF-β1表型中的关键作用。他们还证明，Egr-1介导的凋亡是TGF-β1诱导的纤维化和重塑的先决条件。
Fibrosis and apoptosis are juxtaposed in pulmonary disorders such as asthma and the interstitial diseases, and transforming growth factor (TGF)-β1 has been implicated in the pathogenesis of these responses. However, the in vivo effector functions of TGF-β1 in the lung and its roles in the pathogenesis of these responses are not completely understood. In addition, the relationships between apoptosis and other TGF-β1–induced responses have not been defined. To address these issues, we targeted bioactive TGF-β1 to the murine lung using a novel externally regulatable, triple transgenic system. TGF-β1 produced a transient wave of epithelial apoptosis that was followed by mononuclear-rich inflammation, tissue fibrosis, myofibroblast and myocyte hyperplasia, and septal rupture with honeycombing. Studies of these mice highlighted the reversibility of this fibrotic response. They also demonstrated that a null mutation of early growth response gene (Egr)-1 or caspase inhibition blocked TGF-β1–induced apoptosis. Interestingly, both interventions markedly ameliorated TGF-β1–induced fibrosis and alveolar remodeling. These studies illustrate the complex effects of TGF-β1 in vivo and define the critical role of Egr-1 in the TGF-β1 phenotype. They also demonstrate that Egr-1–mediated apoptosis is a prerequisite for TGF-β1–induced fibrosis and remodeling.
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影响因子：
4.4
作者：
Hagimoto, N;Kuwano, K;Hara, N
通讯作者：
Hara, N
影响因子：
3.6
作者：
Bahouth, SW;Beauchamp, MJ;Vu, KN
通讯作者：
Vu, KN
DOI：
10.1165/rcmb.2002-0009oc
发表时间：
2002-10-01
影响因子：
6.4
作者：
Belperio, JA;Dy, M;Keane, MP
通讯作者：
Keane, MP
影响因子：
30.5
作者：
Corry, DB;Rishi, K;Kheradmand, F
通讯作者：
Kheradmand, F
影响因子：
3.4
作者：
Barnes, PJ
通讯作者：
Barnes, PJ