Blocking follistatin-like 1 attenuates bleomycin-induced pulmonary fibrosis in mice.
Blocking follistatin-like 1 attenuates bleomycin-induced pulmonary fibrosis in mice.
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阻断卵泡抑素样 1 可减轻博莱霉素诱导的小鼠肺纤维化
DOI：
10.1084/jem.20121878
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发表时间：
2015-02-09
期刊：
影响因子：
--
通讯作者：
Ning W
中科院分区：
文献类型：
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作者：
Dong Y;Geng Y;Li L;Li X;Yan X;Fang Y;Li X;Dong S;Liu X;Li X;Yang X;Zheng X;Xie T;Liang J;Dai H;Liu X;Yin Z;Noble PW;Jiang D;Ning W
卵泡抑素样蛋白1(FSTL1)是针对肺损伤而诱导的，通过调节转化生长因子-β和骨形态发生蛋白促进肌成纤维细胞的聚集和随后的纤维化。在小鼠体内减少FSTL1可减少博莱霉素诱导的体内纤维化，为进行性肺纤维化提供潜在的治疗靶点。进行性组织纤维化是导致主要发病率和死亡率的原因之一。肺纤维化是一种上皮-间充质病变，转化生长因子-β-1在其发病机制中起核心作用。在这里，我们发现卵泡抑素样蛋白1(FSTL1)对转化生长因子-β和骨形态发生蛋白信号有不同的调节作用，导致上皮损伤和成纤维细胞的激活。小鼠FSTL1的单倍体缺失或用中和抗体阻断小鼠的FSTL1可减少博莱霉素诱导的体内纤维化。FSTL1是对肺损伤的反应而诱导的，并促进肌成纤维细胞的积聚和随后的纤维化。这些数据提示FSTL1可能成为治疗进行性肺纤维化的一个新的治疗靶点。
Follistatin-like 1 (Fstl1) is induced in response to lung injury and promotes the accumulation of myofibroblasts and subsequent fibrosis via regulation of TGF-β and BMP. Reducing Fstl1 in mice reduces bleomycin-induced fibrosis in vivo, offering a potential therapeutic target for progressive lung fibrosis. Progressive tissue fibrosis is a cause of major morbidity and mortality. Pulmonary fibrosis is an epithelial-mesenchymal disorder in which TGF-β1 plays a central role in pathogenesis. Here we show that follistatin-like 1 (FSTL1) differentially regulates TGF-β and bone morphogenetic protein signaling, leading to epithelial injury and fibroblast activation. Haplodeletion of Fstl1 in mice or blockage of FSTL1 with a neutralizing antibody in mice reduced bleomycin-induced fibrosis in vivo. Fstl1 is induced in response to lung injury and promotes the accumulation of myofibroblasts and subsequent fibrosis. These data suggest that Fstl1 may serve as a novel therapeutic target for treatment of progressive lung fibrosis.