Follistatin like-1 (Fstl1) is required for the normal formation of lung airway and vascular smooth muscle at birth

Fstl1, a secreted protein of the BMP antagonist class, has been implicated in the regulation of lung development and alveolar maturation. Here we generated a Fstl1-lacZ reporter mouse line as well as a Fstl1 knockout allele. We localized Fstl1 transcript in lung smooth muscle cells and identified Fstl1 as essential regulator of lung smooth muscle formation. Deletion of Fstl1 in mice led to postnatal death as a result of respiratory failure due to multiple defects in lung development. Analysis of the mutant phenotype showed impaired airway smooth muscle (SM) manifested as smaller SM line in trachea and discontinued SM surrounding bronchi, which were associated with decreased transcriptional factors myocardin/serum response factor (SRF) and impaired differentiation of SM cells. Fstl1 knockout mice also displayed abnormal vasculature SM manifested as hyperplasia SM in pulmonary artery. This study indicates a pivotal role for Fstl1 in early stage of lung airway smooth muscle development.

卵泡抑素样蛋白1（Fstl1）属于骨形态发生蛋白（BMP）拮抗剂类分泌蛋白，既往研究表明其参与肺发育与肺泡成熟的调控过程。本研究构建了Fstl1-lacZ报告基因小鼠品系，并获得了Fstl1敲除等位基因。研究人员明确了Fstl1转录本定位于肺平滑肌细胞，并证实Fstl1是肺平滑肌形成的关键调控因子。小鼠体内Fstl1基因敲除后，会因肺发育存在多重缺陷引发呼吸衰竭，进而导致出生后死亡。对突变表型的分析显示，气道平滑肌（SM）功能受损，具体表现为气管内平滑肌层厚度减小、支气管周围平滑肌连续性中断，这与心肌素/血清反应因子（SRF）转录因子表达下调以及平滑肌细胞分化受损密切相关。此外，Fstl1敲除小鼠还出现了血管平滑肌异常，具体表现为肺动脉平滑肌增生。本研究揭示了Fstl1在肺气道平滑肌发育早期阶段的关键作用。