Research Area C: Angiogenesis and Alveogenesis
| Research Area Leaders | |
|---|---|
|
This e-mail address is being protected from spambots. You need JavaScript enabled to view it.
Edinger Institute Goethe University Frankfurt Theodor-Stern-Kai 7 60590 Frankfurt |
This e-mail address is being protected from spambots. You need JavaScript enabled to view it.
ECCPS Justus-Liebig-University Giessen Aulweg 130 35392 Giessen |
| Faculty involved | ||||
|---|---|---|---|---|
| T. Acker | A. Acker-Palmer | S. Bellusci | R.P. Brandes | T. Braun |
| B. Brüne | E. Chavakis | S. Dimmeler | J. Eble | I. Fleming |
| A. Günther | B. Jungblut | M. Krüger | S. Liebner | R.E. Morty |
| K.H. Plate | M. Potente | K.T. Preissner | Y. Reiss | M. Schmidt |
| M. Tjwa | C. Urbich | R. Voswinckel | A. Weigert | N. Weissmann |
Summary
Angiogenesis and alveogenesis are interconnected during development as well as during repair after injury and share common signalling pathways. ECCPS members have elucidated the roles of important regulators of endothelial signalling and angiogenesis; such as histone deacetylases and microRNA species, as well as novel ligands and receptors (Notch ligands, EphrinB2), in retinal development and physiological/ pathophysiological angiogenesis. However, our understanding of the dynamic structure and function of endothelial cells and their interaction with matrix and mural cells that lead to vessel and lung maturation is still limited. Particularly, the processes involved in alveogenesis are unclear.This area aims to identify several novel aspects of angiogenesis and alveogenesis in development and disease by focussing on
- the signalling networks that direct and adjust endothelial tip, stalk and phalanx cell behaviour,
- novel modulators of angiogenic blood vessel growth (e.g. Wnt members, lipid metabolites, extracellular RNA),
- the regulation and function of cell-to-cell and cell-to-matrix interactions particularly by integrins, and
- the molecular and cellular basis of secondary septa formation during alveogenesis and regeneration, placing emphasis on detecting parallels between angiogenesis and alveogenesis.
Most relevant publications of the Research Area C
1. Kaluza D, Kroll J, Gesierich S, Yao SP, Tjwa M, Rössig L, Seto E, Schreiber SL, Augustin H, Zeiher AM, Dimmeler S, Urbich U. Class IIb HDAC6 regulates endothelial cell migration and angiogenesis by deacetylation of cortactin EMBO J. In press 2011
2. Boeckel N, Guarani V, Koyanagi M, Röxe T, Lengeling A, Schermuly RT, Gellet P, Braun T, Zeiher A, Dimmeler S: Jumonji domain-containing protein 6 (Jmjd6) is required for angiogenic sprouting and regulates splicing of VEGF-receptor 1. Proc Natl Acad Sci USA 108:3276-81, 2011
3. Clauss M*, Voswinckel R*, Rajashekhar G, Sigua NL, Fehrenbach H, Rush NI, Schweitzer KS, Yildirim AÖ, Kamocki K, Fisher AJ, Gu Y, Safadi B, Nikam S, Hubbard WC, Tuder RM, Twigg HL 3rd, Presson RG, Sethi S, Petrache I. Lung endothelial monocyte-activating protein 2 is a mediator of cigarette smoke-induced emphysema in mice. J Clin Invest 121:2470-9, 2011 *contributed equally
4. Guarani V, Deflorian G, Franco CA, Kruger M, Phng LK, Bentley K, Toussaint L, Dequiedt F, Mostoslavsky R, Schmidt MH, Zimmermann B, Brandes RP, Mione M, Westphal CH, Braun T, Zeiher AM, Gerhardt H, Dimmeler S, Potente M. Acetylation-dependent regulation of endothelial Notch signalling by the SIRT1 deacetylase. Nature 473: 234-8, 2011
5. Kneidinger N, Yildirim AÖ, Callegari J, Takenaka S, Stein MM, Dumitrascu R, Bohla A, Bracke KR, Morty RE, Brusselle GG, Schermuly RT, Eickelberg O, Königshoff M. Activation of the WNT/β-catenin pathway attenuates experimental emphysema. Am J Respir Crit Care Med 183:723-33, 2011
6. Senturk A, Pfennig S, Weiss A, Burk K, Acker-Palmer A. EphrinBs are functional co-receptors for Reelin to regulate neuronal migration. Nature 472: 356-360, 2011
7. Doebele C, Bonauer A, Fischer A, Scholz A, Reiss Y, Urbich C, Hofmann WK, Zeiher AM, Dimmeler S. Members of the microRNA-17-92 cluster exhibit a cell intrinsic anti-angiogenic function in endothelial cells. Blood 115:4944-50, 2010
8. Henze AT, Riedel J, Diem T, Wenner J, Flamme I, Pouyseggur J, Plate KH, Acker T. Prolyl hydroxylases 2 and 3 act in gliomas as protective negative feedback regulators of hypoxia-inducible factors. Cancer Res 70:357-66, 2010
9. Sawamiphak S, Ritter M, Acker-Palmer A. Preparation of retinal explant cultures to study ex vivo tip endothelial cell responses. Nat Protoc 5:1659-65, 2010
10. Sawamiphak S, Seidel S, Essmann CL, Wilkinson GA, Pitulescu M, Acker T, Acker-Palmer A. EphrinB2 regulates VEGFR2 function in developmental and tumour angiogenesis. Nature 65:487-91, 2010
11. Bonauer A, Carmona G, Iwasaki M, Mione M, Koyanagi M, Fischer A, Burchfield J, Fox H, Doebele C, Ohtani K, Chavakis E, Potente M, Tjwa M, Urbich C, Zeiher A, Dimmeler S. MicroRNA-92a controls angiogenesis and functional recovery of ischemic tissues in mice. Science 324;1710-3, 2009
12. Gupte VV, Ramasamy SK, Reddy R, Lee J, Weinreb PH, Violette SM, Guenther A, Warburton D, Driscoll B, Minoo P, Bellusci S. Overexpression of fibroblast growth factor-10 during both inflammatory and fibrotic phases attenuates bleomycin-induced pulmonary fibrosis in mice. Am J Respir Crit Care Med 180: 424-36, 2009
13. Kumarasamy A, Schmitt I, Nave AH, Reiss I, van der Horst I, Dony E, Roberts JD Jr, de Krijger RR, Tibboel D, Seeger W, Schermuly RT, Eickelberg O, Morty RE. Lysyl oxidaseactivity is dysregulated during impaired alveolarization of mouse and human lungs. Am J Respir Crit Care Med 180:1239-52, 2009
14. Schmidt MH, Bicker F, Nikolic I, Meister J, Babuke T, Piciric S, Muller-Esterl W, Plate KH, Dikic I. Epidermal growth factor-like 7 (EGFL7) modulates Notch signaling and effects neural stem cell renewal. Nat Cell Biol 11:873-80, 2009
15. Urbich C, Rossig L, Kaluza D, Potente M, Boeckel JN, Knau A, Diehl F, Geng JG, Hofmann WK, Zeiher AM, Dimmeler S. HDAC5 is a repressor of angiogenesis and determines the angiogenic gene expression pattern of endothelial cells. Blood 113:5669-79, 2009
16. Bellusci S. Lung Stem cells in the balance. Nat Genet 40: 822-4, 2008
17. Chavakis E, Carmona G, Urbich C, Göttig S, Henschler R, Penninger JM, Zeiher AM, Chavakis T, Dimmeler S. Phosphatidylinositol-3-kinase-gamma is integral to homing functions of progenitor cells. Circ Res 102:942-9, 2008
18. Essmann CL, Martinez E, Geiger JC, Zimmer M, Traut MH, Stein V, Klein R, Acker-Palmer A. Serine phosphorylation of ephrinB2 regulates trafficking of synaptic AMPA receptors. Nat Neurosci 11:1035-43, 2008
19. Liebner S, Corada M, Bangsow T, Babbage J, Taddei A, Czupalla CJ, Reis M, Felici A, Wolburg H, Fruttiger M, Taketo MM, von Melchner H, Plate KH, Gerhardt H, Dejana E. Wnt/beta catenin signaling controls development of the blood-brain barrier. J Cell Biol 183:409-417, 2008 IF
20. Martin M*, Potente M*, Janssens V, Vertommen D, Twizere JC, Rider MH, Goris J, Dimmeler S, Kettmann R, Dequiedt F. Protein phosphatase 2A controls the activity of histone deacetylase 7 during T cell apoptosis and angiogenesis. Proc Natl Acad Sci USA 105:4727-4732, 2008 *contribtued equally
21. Taddei A, Giampietro C, Conti A, Orsenigo F, Breviario F, Pirazzoli V, Potente M, Daly C, Dimmeler S, Dejana E. Endothelial adherens junctions control tight junctions by VE-cadherin-mediated upregulation of claudin-5. Nat Cell Biol 10:923-34, 2008
22. Ceteci F, Ceteci S, Karreman C, Kramer BW, Asan E, Götz R, Rapp UR. Disruption of tumor cell adhesion promotes angiogenic switch and progression to micrometastasis in RAF-driven murine lung cancer. Cancer Cell. 12:145-59, 2007
23. Fischer S, Gerriets T, Wessels C, Walberer M, Kostin S, Stolz E, Zheleva K, Hocke A, Hippenstiel S, Preissner KT. Extracellular RNA mediates endothelial cell permeability via vascular endothelial growth factor. Blood 110:2457-2465, 2007
24. Fisslthaler B, Fleming I, Keserü B, Walsh K, Busse R. Fluid shear stress and NO decrease the activity of the hydroxy-methylglutaryl coenzyme A reductase in endothelial cells via the AMP-activated protein kinase and FoxO1. Circ Res 100:e12-e21, 2007
25. Kuehbacher A, Urbich C, Zeiher AM, Dimmeler S. Role of Dicer and Drosha for endothelial microRNA expression and angiogenesis. Circ Res 101:59-68, 2007
26. Potente M, Ghaeni L, Baldessari D, Mostoslavsky R, Rossig L, Dequiedt F, Haendeler J, Mione M, Dejana E, Alt FW, Zeiher AM, Dimmeler S. SIRT1 controls endothelial angiogenic functions during vascular growth. Genes Dev 21:2644-58, 2007
27. Ramasamy K, Mailleux AA, Gupte V, Mata F, Sala GF, Veltmaat JM, del Moral PM, De Langhe S, Parsa S, Kelly L, Kelly R, Keshet E, Minoo P, Warburton D, Bellusci S. Fgf10 dosage is critical for the amplification of epithelial cell progenitors and for the formation of multiple mesenchymal lineages during lung development. Dev Biol 307:237-47, 2007
28. Reiss Y, Droste J, Heil M, Tribulova S, Schmidt MH, Schaper W, Dumont DJ Plate KH. Angiopoietin-2 impairs revascularization after limb ischemia. Circ Res 101:88-96, 2007
29. Segura I, Essmann CL, Weinges S, Acker-Palmer A. Grb4 and GIT1 transduce ephrinB reverse signals modulating spine morphogenesis and synapse formation. Nat Neurosci 10(3):301-10, 2007
30. Fiedler U*, Reiss Y*, Scharpfenecker M, Grunow V, Koidl S, Thurston G, Gale NW, Witzenrath M, Rosseau S, Suttorp N, Sobke A, Herrmann M, Preissner KT, Vajkoczy P, Augustin HG. Angiopoietin-2 sensitizes endothelial cells to TNF-a and has a crucial role in the induction of inflammation. Nat Med 12:235-39, 2006 *contribtued equally