Li Xiaohe, Fang Yinshan, Li Xue, Liang Jiurong, Jiang Dianhua, Geng Yan, Ning Wen
State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin, 300071, China.
Cedars-Sinai Medical Center, Department of Medicine, Los Angeles, CA, 90048, United States of America.
PLoS One. 2016 Jun 29;11(6):e0158385. doi: 10.1371/journal.pone.0158385. eCollection 2016.
Follistatin-like 1 (FSTL1) is a secreted bone morphogenetic protein (BMP) antagonist, and it plays a crucial role in normal lung development. Deletion of Fstl1 leads to postnatal death in mice due to respiratory failure. To further explore the role of FSTL1 in mouse lung development, we created a transgene SFTPC-Fstl1 allele mouse displaying significant epithelial overexpression of Fstl1 in all stages of lung development. However, epithelial overexpression of Fstl1 did not alter lung morphogenesis, epithelial differentiation and lung function. Moreover, we found that FSTL1 function was blocked by the epithelial polarization, which was reflected by the remarkable apical secretion of FSTL1 and the basolateral BMP signaling. Taken together, this study demonstrates that tightly spatial interaction of FSTL1 and BMP signaling plays an essential role in lung development.
类卵泡抑素1（FSTL1）是一种分泌型骨形态发生蛋白（BMP）拮抗剂，在正常肺发育中起关键作用。Fstl1基因缺失会导致小鼠出生后因呼吸衰竭而死亡。为了进一步探究FSTL1在小鼠肺发育中的作用，我们构建了一个转基因SFTPC-Fstl1等位基因小鼠，该小鼠在肺发育的各个阶段均表现出Fstl1在上皮细胞中的显著过表达。然而，Fstl1在上皮细胞中的过表达并未改变肺形态发生、上皮分化和肺功能。此外，我们发现FSTL1的功能被上皮极化所阻断，这表现为FSTL1显著的顶端分泌和基底外侧BMP信号传导。综上所述，本研究表明FSTL1与BMP信号传导的紧密空间相互作用在肺发育中起重要作用。
