Nemo-like kinase regulates the expression of vascular endothelial growth factor (VEGF) lein alveolar epithelial cells

作者:Ke Hengning; Masoumi Katarzyna Chmielarska; Ahlqvist Kristofer; Seckl Michael J; Rydell Tormanen Kristina; Massoumi Ramin*
来源:Scientific Reports, 2016, 6(1): 23987.
DOI:10.1038/srep23987

摘要

The canonical Wnt signaling can be silenced either through beta-catenin-mediated ubiquitination and degradation or through phosphorylation of Tcf and Lef by nemo-like kinase (NLK). In the present study, we generated NLK deficient animals and found that these mice become cyanotic shortly before death because of lung maturation defects. NLK-/- lungs exhibited smaller and compressed alveoli and the mesenchyme remained thick and hyperplastic. This phenotype was caused by epithelial activation of vascular endothelial growth factor (VEGF) via recruitment of Lef1 to the promoter of VEGF. Elevated expression of VEGF and activation of the VEGF receptor through phosphorylation promoted an increase in the proliferation rate of epithelial and endothelial cells. In summary, our study identifies NLK as a novel signaling molecule for proper lung development through the interconnection between epithelial and endothelial cells during lung morphogenesis.

  • 出版日期2016-4-1