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BMP9 and BMP10 pair in the bloodstream

​Cancer Biology and Infection laboratory researchers are studying how Bone Morphogenetic Proteins (BMPs) control the development and stability of blood vessels. Deregulation of these signaling pathways leads to serious vascular diseases such as Rendu-Osler's disease, or pulmonary arterial hypertension, for which there is currently no curative treatment.

Published on 3 August 2018
Bone Morphogenetic Proteins (BMPs) are major players in the development of multicellular organisms. These proteins are actually growth factors that control organogenesis in the embryo, but are also necessary to maintain the organization of tissues in adults. BMP9 and BMP10 are the ALK1 (Activin receptor-Like Kinase 1) ligands and are key regulators of vascular remodeling, but their respective biological activities are still a matter of debate.

BMP9 and BMP10 proteins were identified about 10 years ago [1-2] by the team « BMP family in angiogenesis and lymphangiogenesis » of the Biology of Cancer and Infection laboratory. These are key molecules involved in maintaining the quiescence of the blood vascular network. BMP9 is produced by the liver, and previous work has shown that this molecule circulates in the blood in an active form. BMP10 is produced by the heart and has a vital role in cardiac development. It is also found in the blood but it circulates under an inactive form.

The work published by this same team [3] revisits these concepts, demonstrating that the active form that circulates in the blood is in fact a heterodimer of BMP9 and BMP10. The biosynthesis of this molecule takes place in specific cells of the liver called stellate cells. Indeed, the team members demonstrated, using the RNAscope® technique, that stellate cells express both BMP9 and BMP10. The BMP9-10 heterodimer is then secreted in the bloodstream. It can then activate the endothelial cells in order to control the organization of the blood network.

Understanding the respective functions of the homo- or heterodimeric forms of these BMPs represents a new challenge and an important step for the development of treatments of vascular diseases associated with genetic defects of this signaling pathway.

In vivo BMP9 and BMP10 biosynthesis model:
BMP9 and BMP10 are synthesized in a homodimeric form, respectively by the liver and the heart. The liver also biosynthesizes the heterodimer BMP9-10, a newly characterized form, which is active form on endothelial cells lining the blood vessels.

*Mutations of ALK1 are responsible for a rare vascular disease, Hereditary Hemorrhagic Telangiectasia (HHT) which is characterized by nosebleeds, mucosal blood vessel dilations and arteriovenous malformations.

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