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Bone morphogenetic protein 9 (BMP9) controls lymphatic vessel maturation and valve formation
Sandrine Levet1, Delphine Ciais, Galina Merdzhanova
1INSERM U1036, Grenoble, France.
Blood
|June 7, 2013
Summary
Bone morphogenetic protein 9 (BMP9) is crucial for lymphatic development, regulating lymphatic vessel maturation and valve formation. BMP9 deficiency impairs lymphatic function and fluid homeostasis.
Area of Science:
- Vascular Biology
- Developmental Biology
- Molecular Medicine
Background:
- Lymphatic vessels are vital for tissue fluid balance, and their dysfunction is linked to human diseases.
- Activin receptor-like kinase 1 (ALK1), a TGF-β receptor, is present on lymphatic endothelial cells (LECs).
- Bone morphogenetic protein 9 (BMP9), an ALK1 ligand, is known for its role in retinal angiogenesis.
Purpose of the Study:
- To investigate the role of BMP9 in lymphatic development and function.
- To determine if BMP9 influences lymphatic endothelial cell behavior and lymphatic valve formation.
Main Methods:
- Utilized Bmp9-knockout (KO) mouse models to study lymphatic development.
- Analyzed mesenteric lymphatic vessels for hyperplasia, LYVE-1 expression, and valve formation.
- Investigated BMP9's effect on LYVE-1 expression and gene regulation in LECs in an ALK1-dependent manner.
- Assessed lymphatic draining efficiency in Bmp9-KO mice.
Main Results:
- Bmp9 deficiency in mice led to abnormal lymphatic development, including hyperplastic mesenteric collecting vessels.
- BMP9 inhibited LYVE-1 expression in LECs via ALK1.
- Bmp9-KO mice showed reduced lymphatic valve number and maturation.
- BMP9 upregulated key genes involved in lymphatic valve formation (Foxc2, Connexin37, EphrinB2, Neuropilin1) in LECs.
- Bmp9-KO mice exhibited decreased lymphatic draining efficiency.
Conclusions:
- BMP9 is an essential extracellular regulator of lymphatic vascular network maturation.
- BMP9 plays a critical role in lymphatic valve development and overall lymphatic vessel function.
- Dysregulation of BMP9 signaling can lead to impaired lymphatic fluid homeostasis.
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