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Updated: Mar 23, 2026
A Simple Bioassay for the Evaluation of Vascular Endothelial Growth Factors
Published on: March 15, 2016
Nemo-like kinase regulates the expression of vascular endothelial growth factor (VEGF) in alveolar epithelial cells
Hengning Ke1, Katarzyna Chmielarska Masoumi1, Kristofer Ahlqvist1
1Molecular Tumor Pathology, Department of Laboratory Medicine, Lund University, Sweden.
Abstract:
The canonical Wnt signaling can be silenced either through β-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.
Insights
Nemo-like kinase (NLK) deficiency causes lung maturation defects, leading to smaller alveoli and respiratory distress. This study reveals NLK
Area of Science:
- Developmental Biology
- Molecular Signaling
- Pulmonary Medicine
Background:
- Canonical Wnt signaling regulates cell fate and tissue development.
- Wnt signaling can be inhibited by nemo-like kinase (NLK) through Tcf/Lef phosphorylation.
- Proper lung development relies on intricate epithelial-endothelial cell crosstalk.
Purpose of the Study:
- To investigate the role of nemo-like kinase (NLK) in lung development.
- To elucidate the molecular mechanisms underlying NLK-mediated lung morphogenesis.
- To understand the link between Wnt signaling inhibition and lung maturation.
Main Methods:
- Generation and analysis of nemo-like kinase (NLK)-deficient mice.
- Histological examination of NLK-/- lung tissues to assess alveolar and mesenchymal development.
- Molecular analysis of gene expression, including vascular endothelial growth factor (VEGF) and its signaling pathway.
Main Results:
- NLK-deficient mice exhibit cyanosis and severe lung maturation defects, characterized by compressed alveoli and hyperplastic mesenchyme.
- NLK deficiency leads to epithelial activation of VEGF expression via Lef1 recruitment to the VEGF promoter.
- Upregulated VEGF signaling promotes increased proliferation of lung epithelial and endothelial cells.
Conclusions:
- Nemo-like kinase (NLK) is essential for normal lung development and maturation.
- NLK regulates lung morphogenesis by controlling the epithelial-endothelial cell communication axis through VEGF signaling.
- Targeting NLK or downstream VEGF pathways may offer therapeutic strategies for lung developmental disorders.
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