Follistatin like-1 aggravates silica-induced mouse lung injury.
Follistatin like-1 aggravates silica-induced mouse lung injury.
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Follistatin like-1 加重硅诱导的小鼠肺损伤
DOI：
10.1038/s41598-017-00478-0
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发表时间：
2017-03-24
影响因子：
4.6
通讯作者：
Ning W
中科院分区：
文献类型：
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作者：
Fang Y;Zhang S;Li X;Jiang F;Ye Q;Ning W
在工作场所长时间职业性吸入粉尘，如结晶二氧化硅，导致世界范围内的纤维化肺病。这些疾病的潜在机制尚不清楚，因此对这些疾病没有有效的治疗方法。我们发现在矽肺患者血清和矽尘诱导的小鼠模型肺中，卵泡抑素样1（FSTL 1）水平升高。诱导的Fstl 1通过激活IL-1β样受体家族、含有3v（NLRP 3）的pyrin结构域的炎性小体介导的巨噬细胞产生IL-1β来调节炎症反应。同时，Fstl 1通过正性调节TGF-β1信号通路促进纤维化。Fstl 1单倍不足或用中和抗体阻断FSTL 1对小鼠体内二氧化硅诱导的肺损伤具有保护作用。我们的数据表明Fstl 1在肺纤维化中发挥重要作用，并可能作为治疗硅肺的新治疗靶点。
Occupational inhalation of dust, such as crystalline silica, for prolonged periods in the workplace leads to fibrotic lung diseases worldwide. The mechanisms underlying the diseases are unknown, so that no effective treatment exists for these conditions. We found elevated levels of follistatin like 1 (FSTL1) in serum from patients with silicosis and in lungs from silica-induced mouse model. The induced Fstl1 regulated inflammation response via activation of nod-like receptor family, pyrin domain containing 3v (NLRP3) inflammasome-mediated IL-1β production from macrophages. Meanwhile, Fstl1 promoted fibrosis via positive regulation of TGF-β1 signaling. Haploinsufficiency of Fstl1 or blockage of FSTL1 with a neutralizing antibody was protective from silica-induced lung injury in mice in vivo. Our data suggest that Fstl1 plays an important role in lung fibrosis, and may serve as a novel therapeutic target for treatment of silicosis.