Metallothionein 2 regulates endothelial cell migration through transcriptional regulation of vegfc expression

Analysis of developmental angiogenesis can help to identify regulatory networks, which also contribute to disease-related vascular growth. Vascular endothelial growth factors (Vegf) drive angiogenic processes such as sprouting, endothelial cell (EC) migration and proliferation. However, how Vegf exp...

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Bibliographic Details
Published in:Angiogenesis (London) 2015-10, Vol.18 (4), p.463-475
Main Authors: Schuermann, Annika, Helker, Christian S. M., Herzog, Wiebke
Format: Article
Language:English
Subjects:
Animals
Biomedical and Life Sciences
Biomedicine
Cancer Research
Cardiology
Cell Biology
Cell Movement - physiology
Endothelial Cells - cytology
Endothelial Cells - metabolism
Gene Expression Regulation, Developmental - physiology
Metallothionein - genetics
Metallothionein - metabolism
Neovascularization, Physiologic - physiology
Oncology
Ophthalmology
Original Paper
Transcription, Genetic - physiology
Vascular Endothelial Growth Factor C - biosynthesis
Vascular Endothelial Growth Factor C - genetics
Zebrafish - genetics
Zebrafish - metabolism
Zebrafish Proteins - biosynthesis
Zebrafish Proteins - genetics
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Summary:Analysis of developmental angiogenesis can help to identify regulatory networks, which also contribute to disease-related vascular growth. Vascular endothelial growth factors (Vegf) drive angiogenic processes such as sprouting, endothelial cell (EC) migration and proliferation. However, how Vegf expression is regulated during development is not well understood. By analyzing developmental zebrafish angiogenesis, we have identified Metallothionein 2 (Mt2) as a novel regulator of vegfc expression. While Metallothioneins (Mts) have been extensively analyzed for their capability of regulating homeostasis and metal detoxification, we demonstrate that Mt2 is required for EC migration, proliferation and angiogenic sprouting upstream of vegfc expression. We further demonstrate that another Mt family member cannot compensate Mt2 deficiency and therefore postulate that Mt2 regulates angiogenesis independent of its canonical Mt function. Our data not only reveal a non-canonical function of Mt2 in angiogenesis, but also propose Mt2 as a novel regulator of vegfc expression.
ISSN:0969-6970
1573-7209
DOI:10.1007/s10456-015-9473-6