BMP9 and BMP10, two new key players in blood and lymphatic vascular development
Event details
| Date | 24.08.2015 |
| Hour | 13:30 › 14:30 |
| Speaker | Sabine Bailly |
| Location | |
| Category | Conferences - Seminars |
Laboratoire de Biologie du Cancer et de l’Infection, INSERM U1036-CEA-Grenoble/Université Grenoble-Alpes
BMP9 (Bone Morphogenetic Proteins) and BMP10 are two members of the TGFß superfamily. In 2007, our team demonstrated that they bind with high affinity to the receptor ALK1 (activin receptor-like kinase 1), a receptor specifically expressed on blood and lymphatic endothelial cells1 that plays a key role in vascular development.
BMP9 and BMP10 are both present in blood and, we have recently shown that they play critical and specific roles in blood and lymphatic development. Using Bmp9 knockout mice, we found that Bmp9 inactivation had no significant effect on blood vascularization of mouse retina, however addition of a neutralizing anti-BMP10 antibody strongly affected retinal vascularization (inhibition of vascular radial expansion and increase in vessel density) in Bmp9 knockout mice but not in WT mice2, demonstrating that BMP9 and BMP10 play a redundant role in retinal vascularization. We also found that they play a redundant role in vascular remodeling of larger vessels such as the ductus arteriosus, which plays a key role at birth allowing pulmonary circulation3. On the other hand, Bmp9 knockout mice were defective in lymphatic valve formation and lymphatic maturation4, demonstrating a specific role for BMP9 in lymphatic development. BMP9 and BMP10 are also associated to vascular diseases. Indeed, we could show that some mutations in ALK1 or its co-receptor endoglin identified in HHT (hemorrhagic hereditary telangiectasia) patients can lead to a defect in BMP9 or BMP10 binding5, 6. We were also able to propose that an anti-angiogenic treatment could be beneficial to HHT patients7.
Taken together, these results clearly demonstrate that the BMP9/BMP10/ALK1 is an emerging vascular signaling pathway with potential therapeutic applications. A better understanding of the respective roles of these two BMPs is thus strongly needed in order to bring some new therapeutic approaches in the treatment of vascular diseases but also in tumor angiogenesis and lymphangiogenesis.
1. David L, et al. Blood. 2007;109:1953-1961
2. Ricard N, et al. Blood. 2012;119:6162-6171
3. Levet S, et al. PNAS 2015;112:E3207-3215
4. Levet S, et al. Blood. 2013;122:598-607
5. Ricard N, et al. Blood. 2010;116:1604-1612
6. Mallet C, et al. Hum Mol Genet. 2015;24:1142-1154
7. Dupuis-Girod S, et al. JAMA. 2012;307:948-955
BMP9 (Bone Morphogenetic Proteins) and BMP10 are two members of the TGFß superfamily. In 2007, our team demonstrated that they bind with high affinity to the receptor ALK1 (activin receptor-like kinase 1), a receptor specifically expressed on blood and lymphatic endothelial cells1 that plays a key role in vascular development.
BMP9 and BMP10 are both present in blood and, we have recently shown that they play critical and specific roles in blood and lymphatic development. Using Bmp9 knockout mice, we found that Bmp9 inactivation had no significant effect on blood vascularization of mouse retina, however addition of a neutralizing anti-BMP10 antibody strongly affected retinal vascularization (inhibition of vascular radial expansion and increase in vessel density) in Bmp9 knockout mice but not in WT mice2, demonstrating that BMP9 and BMP10 play a redundant role in retinal vascularization. We also found that they play a redundant role in vascular remodeling of larger vessels such as the ductus arteriosus, which plays a key role at birth allowing pulmonary circulation3. On the other hand, Bmp9 knockout mice were defective in lymphatic valve formation and lymphatic maturation4, demonstrating a specific role for BMP9 in lymphatic development. BMP9 and BMP10 are also associated to vascular diseases. Indeed, we could show that some mutations in ALK1 or its co-receptor endoglin identified in HHT (hemorrhagic hereditary telangiectasia) patients can lead to a defect in BMP9 or BMP10 binding5, 6. We were also able to propose that an anti-angiogenic treatment could be beneficial to HHT patients7.
Taken together, these results clearly demonstrate that the BMP9/BMP10/ALK1 is an emerging vascular signaling pathway with potential therapeutic applications. A better understanding of the respective roles of these two BMPs is thus strongly needed in order to bring some new therapeutic approaches in the treatment of vascular diseases but also in tumor angiogenesis and lymphangiogenesis.
1. David L, et al. Blood. 2007;109:1953-1961
2. Ricard N, et al. Blood. 2012;119:6162-6171
3. Levet S, et al. PNAS 2015;112:E3207-3215
4. Levet S, et al. Blood. 2013;122:598-607
5. Ricard N, et al. Blood. 2010;116:1604-1612
6. Mallet C, et al. Hum Mol Genet. 2015;24:1142-1154
7. Dupuis-Girod S, et al. JAMA. 2012;307:948-955
Practical information
- Informed public
- Free
Organizer
- Daniel Constam
Contact
- Daniel Constam