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Status |
Public on Oct 07, 2020 |
Title |
BMP/Taz-Hippo signaling modulates VEGF-mediated angiogenesis |
Organism |
Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
The BMP/TGFβ-Smad, Notch and VEGF signaling guides formation of endothelial tip and stalk cells. However, the crosstalk of bone morphogenetic proteins (BMPs) and vascular endothelial growth factor receptor 2 (VEGFR2) signaling has remained largely unknown. We demonstrate that BMP family members regulate VEGFR2 and Notch signaling, and act via TAZ-Hippo signaling pathway. BMPs were found to be regulated after VEGF gene transfer in C57/Bl6 mice and in a porcine myocardial ischemia model. BMPs 2/4/6 were identified as endothelium-specific targets of VEGF. BMP2 modulated VEGF-mediated endothelial sprouting via Delta like Canonical Notch Ligand 4 (DLL4). BMP6 modulated VEGF signaling by regulating VEGFR2 expression and acted via Hippo signaling effector TAZ, known to regulate cell survival/proliferation, and to be dysregulated in cancer. In a matrigel plug assay in nude mice BMP6 was further demonstrated to induce angiogenesis. BMP6 is the first member of BMP family found to directly regulate both Hippo signaling and neovessel formation. It may thus serve as a target in pro/anti-angiogenic therapies.
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Overall design |
Gene expression profiling of mouse liver tissue in response to iv. AdVEGF-A treatment via tail vain injections.
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Contributor(s) |
Laakkonen JP, Niskanen H, Kaikkonen MU |
Citation(s) |
33021694 |
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Submission date |
Jun 01, 2016 |
Last update date |
Oct 09, 2020 |
Contact name |
Henri Niskanen |
Organization name |
University of Eastern Finland
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Department |
A.I. Virtanen Institute
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Street address |
P.O. Box 1627
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City |
Kuopio |
ZIP/Postal code |
FI-70211 |
Country |
Finland |
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Platforms (1) |
GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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Samples (10)
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Relations |
BioProject |
PRJNA324068 |
SRA |
SRP075960 |