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Cited by 22Neonatal Respiratory Health ResearchWnt/β-catenin signaling in development and cancerDevelopmental Biology and Gene Regulation

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

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Ke, Hengning, Masoumi, Katarzyna Chmielarska, Ahlqvist, Kristofer, Seckl, Michael J., Rydell-Törmänen, Kristina, Massoumi, Ramin·2016·Scientific Reports
DOI 10.1038/srep23987PMC PMC4817507
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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.

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  • The lung phenotype in NLK-deficient mice is due to deletion of NLK that cannot phosphorylate LEF1, leading to elevated VEGF expression that causes aberrant proliferation of pulmonary epithelial and endothelial cells.

    “This was due to the deletion of NLK that could not phosphorylated LEF1, which led to elevated levels of VEGF expression that caused aberrant proliferation of pulmonary epithelial and endothelial cells [36].”

    From Nemo-Like Kinase in Development and Diseases: Insights from Mouse Studies (2020) · cites this paper as [36]

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Cited by

Sorted by citations

Authors
Ke, H., Masoumi, K. C., Ahlqvist, K., Seckl, M. J., Rydell-Törmänen, K., & Massoumi, R.
Affiliations
  • Lund University (SE)
  • Imperial College Healthcare NHS Trust (GB)
Corresponding author
Massoumi, Ramin
ORCID
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2016-04-01
Volume
6
Issue
1
Pages
23987-23987
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/srep23987
PMC
PMC4817507
OpenAlex
W2321611378
Cited by
22
References
4
Citations by year
2025: 2 · 2024: 1 · 2023: 1 · 2022: 2 · 2020: 3 · 2019: 2 · 2018: 2 · 2017: 3 · 2016: 5
FWCI
3.58
Type
journal article
Language
en
Open access
Licence
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Lund University Publications (Lund University) (submittedVersion)
  • Spiral (Imperial College London) (submittedVersion, cc-by)
Funders
  • Swedish Cancer Foundation
  • Gyllenstiernska Krapperupsstiftelsen
  • European Commission
  • Gunnar Nilssons Cancerstiftelse
  • Magnus Bergvalls Stiftelse
  • FP7 Ideas: European Research Council (260460)
Topics
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Neonatal Respiratory Health Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
Keywords
Nemo-like kinase, vascular endothelial growth factor, LEF1, Wnt/β-catenin signaling, lung development, alveolar epithelial cells, lung morphogenesis, cyanosis, alveolar hyperplasia
MeSH terms
Animals, Cells, Cultured, Enzyme-Linked Immunosorbent Assay, Exons, Fibroblasts, Humans, Lung, Mutation, Phenotype, Phosphorylation, Promoter Regions, Genetic, Protein Serine-Threonine Kinases, Genes, Reporter, Mice, Knockout, Platelet Endothelial Cell Adhesion Molecule-1, Mitogen-Activated Protein Kinases, Vascular Endothelial Growth Factor A, Endothelial Cells, Intracellular Signaling Peptides and Proteins, Cell Proliferation, Mice, Lymphoid Enhancer-Binding Factor 1, Alveolar Epithelial Cells, Wnt Signaling Pathway

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