Charakterisierung von BMPER in der Blutgefässentwicklung und bei vaskuären Erkrankungen
Final Report Abstract
The project "Role of BMPER in vascular health and disease" elucidated the regulation and expression of BMPER in cardiovascular diseases. We were able to position the novel protein BMPER within known signaling cascades and demonstrated that BMPER holds a key role in important diseases such as vascular inflammation. Taken the data together, the novel protein BMPER was identified as a protective player in vascular inflammation. Loss of BMPER results in a pro-inflammative state whereas excess BMPER reduces vascular inflammation. We have extended these insights to lung epithelium and found that similar principles hold true. BMPER has a protective role, where as loss of BMPER increases cell damage. As frequently in biologic processes BMPER expression may also be double-edged sword which is demonstrated by our lung tumor experiments. In lung tumors loss of BMPER comes along with reduced tumor cell growth. These findings underline that a detailed understanding of BMPER expression and regulation is necessary to keep a fine-tuned equilibrium between risk and benefit. In the present project we have contributed to this understanding laying the ground for future experiments to further investigate this very promising vascular mediator.
Publications
- BMPER is upregulated by statins and modulates endothelial inflammation by intercellular adhesion molecule-1. Arterioscler Thromb Vasc Biol. 2010 Mar;30:554-560
Helbing T, Rothweiler R, Heinke J, Goetz L, Diehl P, Zirlik A, Patterson C, Bode C, Moser M
- Kruppel-like factor 15 regulates BMPER in endothelial cells. Cardiovasc Res. 2010;85:551-559
Helbing T, Volkmar F, Goebel U, Heinke J, Diehl P, Pahl HL, Bode C, Patterson C and Moser M
- BMP activity controlled by BMPER regulates the proinflammatory phenotype of endothelium. Blood. 2011 Nov 3;118:5040-5049
Helbing T, Rothweiler R, Ketterer E, Goetz L, Heinke J, Grundmann S, Duerschmied D, Patterson C, Bode C, Moser M
- Bone morphogenetic protein modulator BMPER is highly expressed in malignant tumors and controls invasive cell behavior. Oncogene. 2012 Jun 14;31:2919-2930
Heinke J, Kerber M, Rahner S, Mnich L, Lassmann S, Helbing T, Werner M, Patterson C, Bode C, Moser M
(See online at https://doi.org/10.1038/onc.2011.473) - Antagonism and synergy between extracellular BMP modulators Tsg and BMPER balance blood vessel formation. Journal of cell science. 2013 Jul 15;126:3082-3094
Heinke J, Juschkat M, Charlet A, Mnich L, Helbing T, Bode C, Patterson C, Moser M
(See online at https://doi.org/10.1242/jcs.122333) - Inhibition of BMP activity protects epithelial barrier function in lung injury. The Journal of pathology. 2013 Sep;231:105-116
Helbing T, Herold EM, Hornstein A, Wintrich S, Heinke J, Grundmann S, Patterson C, Bode C, Moser M
(See online at https://doi.org/10.1002/path.4215)
