title: Nemo-like kinase regulates the expression of vascular endothelial growth factor (VEGF) in alveolar epithelial cells.
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.
authors.affiliation: Molecular Tumor Pathology, Department of Laboratory Medicine, Lund University, Sweden.
authors.forename: Hengning
authors.initials: H
authors.lastname: Ke
authors.affiliation: Molecular Tumor Pathology, Department of Laboratory Medicine, Lund University, Sweden.
authors.forename: Katarzyna Chmielarska
authors.initials: KC
authors.lastname: Masoumi
authors.affiliation: Molecular Tumor Pathology, Department of Laboratory Medicine, Lund University, Sweden.
authors.forename: Kristofer
authors.initials: K
authors.lastname: Ahlqvist
authors.affiliation: Department of Medical Oncology, Imperial College Healthcare NHS Trust and Imperial College London, London, UK.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Seckl
authors.affiliation: Lung Biology, Department of Experimental Medical Science, Lund University, Sweden.
authors.forename: Kristina
authors.initials: K
authors.lastname: Rydell-Törmänen
authors.affiliation: Molecular Tumor Pathology, Department of Laboratory Medicine, Lund University, Sweden.
authors.forename: Ramin
authors.initials: R
authors.lastname: Massoumi
mesh_terms: D056809:Alveolar Epithelial Cells / Q000166:cytology*; D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology; D004797:Enzyme-Linked Immunosorbent Assay; D005091:Exons; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D017930:Genes, Reporter; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008168:Lung / Q000196:embryology; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D010641:Phenotype; D010766:Phosphorylation; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D011401:Promoter Regions, Genetic; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D060449:Wnt Signaling Pathway
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C497574:Lef1 protein, mouse; D051821:Lymphoid Enhancer-Binding Factor 1; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D042461:Vascular Endothelial Growth Factor A; C470551:NLK protein, human; C408347:Nlk protein, mouse; D017346:Protein Serine-Threonine Kinases; D020928:Mitogen-Activated Protein Kinases