Lymphangiogenomics

 

 
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Endothelial specialization during angiogenic and lymphangiogenic sprouting

 

 

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Last Update: June 23, 2009

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

  

 

 

 

  

 

 

 

 

Very little is known about the cellular mechanisms of lymphatic vessel formation, but EC sprouts have been reported, suggesting similarity with angiogenesis. Angiogenic sprouting requires endothelial decisions concerning where and when to sprout, branch, and fuse. In this project, we address the genetic basis for EC and LEC functional specialization.

 

 

Responsible for this project:

 

 

Dr. Christer Betsholtz

Laboratory of Vascular Biology, Division of Matrix Biology
House A3, Plan 4
Department of Medical Biochemistry and Biophysics
Scheeles vag 2
Karolinska Institutet
SE-171 77 Stockholm, Sweden

Office Phone: +46-8-52487960
Fax:                 +46-8-313445
Email: christer.betsholtz(at)mbb.ki.se

 

 

Selected recent publications:

 

  1. Sun Y, He L, Takemoto M, Patrakka J, Pikkarainen T, Genové G, Norlin J, Truvé K, Tryggvason K, Betsholtz C. Glomerular Transcriptome Changes Associated with Lipopolysaccharide-Induced Proteinuria. Am J Nephrol. 29(6):558-570, 2009.
     
  2. The glomerular transcriptome and a predicted protein-protein interaction network. He L, Sun Y, Takemoto M, Norlin J, Tryggvason K, Samuelsson T, Betsholtz C. J Am Soc Nephrol. 2008 Feb;19(2):260-8.
     
  3. Betsholtz C, He L, Takemoto M, Norlin J, Sun Y, Patrakka J, Tryggvason K. The glomerular transcriptome and proteome. Nephron Exp Nephrol. 106(2):e32-6, 2007.
     
  4. He L, Sun Y, Patrakka J, Mostad P, Norlin J, Xiao Z, Andrae J, Tryggvason K, Samuelsson T, Betsholtz C, Takemoto M. Glomerulus-specific mRNA transcripts and proteins identified through kidney expressed sequence tag database analysis. Kidney Int. 71(9):889-900, 2007.
     

  5. Bjarnegard M, Enge M, Norlin J, Gustafsdottir S, Fredriksson S, Abramsson A, Takemoto M, Gustafsson E, Fassler R, Betsholtz C. Endothelium-specific ablation of PDGFB leads to pericyte loss and glomerular, cardiac and placental abnormalities. Development 131:1847-57, 2004.
     

  6. Karkkainen MJ, Haiko P, Sainio K, Partanen J, Taipale J, Petrova TV, Jeltsch M, Jackson DG, Talikka M, Rauvala H, Betsholtz C, Alitalo K. Vascular endothelial growth factor C is required for sprouting of the first lymphatic vessels from embryonic veins. Nat Immunol 5:74-80, 2004.
     

  7. Abramsson A, Lindblom P, Betsholtz C. Endothelial and nonendothelial sources of PDGF-B regulate pericyte recruitment and influence vascular pattern formation in tumors. J Clin Invest 112:1142-1151, 2003.
     

  8. Lindblom P, Gerhardt H, Liebner S, Abramsson A, Enge M, Hellstrom M, Backstrom G, Fredriksson S, Landegren U, Nystrom HC, Bergstrom G, Dejana E, Ostman A, Lindahl P, Betsholtz C. Endothelial PDGF-B retention is required for proper investment of pericytes in the microvessel wall. Genes Dev 17:1835-1840, 2003.
     

  9. Gerhardt H, Betsholtz C. Endothelial-pericyte interactions in angiogenesis. Cell Tissue Res 314:15-23, 2003.
     

  10. Gerhardt H, Golding M, Fruttiger M, Ruhrberg C, Lundkvist A, Abramsson A, Jeltsch M, Mitchell C, Alitalo K, Shima D, Betsholtz C. VEGF guides angiogenic sprouting utilizing endothelial tip cell filopodia. J Cell Biol 161:1163-1177, 2003.
     

  11. Tocchetti A, Confalonieri S, Scita G, Di Fiore PP, Betsholtz C. In silico analysis of the EPS8 gene family: genomic organization, expression profile, and protein structure. Genomics 81:234-44, 2003.
     

  12. Bondjers C, Kalen M, Hellstrom M, Scheidl SJ, Abramsson A, Renner O, Lindahl P, Cho H, Kehrl J, Betsholtz C. Transcription profiling of platelet-derived growth factor-B-deficient mouse embryos identifies RGS5 as a novel marker for pericytes and vascular smooth muscle cells. Am J Pathol 162:721-729, 2003.
     

  13. Ruhrberg C, Gerhardt H, Golding M, Watson R, Ioannidou S, Fujisawa H, Betsholtz C, Shima DT.
     

  14. Spatially restricted patterning cues provided by heparin-binding VEGF-A control blood vessel branching morphogenesis. Genes Dev 16:2684-2698, 2002.
     

  15. Takemoto M, Asker N, Gerhardt H, Lundkvist A, Johansson BR, Saito Y, Betsholtz C. A new method for large scale isolation of kidney glomeruli from mice. Am J Pathol 161:799-805, 2002.
     

  16. Enge M, Bjarnegard M, Gerhardt H, Gustafsson E, Kalen M, Asker N, Hammes HP, Shani M, Fassler R, Betsholtz C. Endothelium-specific platelet-derived growth factor-B ablation mimics diabetic retinopathy. EMBO J 21:4307-4316, 2002.
     

  17. Bostrom H, Gritli-Linde A, Betsholtz C. PDGF-A/PDGF alpha-receptor signaling is required for lung growth and the formation of alveoli but not for early lung branching morphogenesis. Dev Dyn 223:155-162, 2002.
     

  18. Abramsson A, Berlin O, Papayan H, Paulin D, Shani M, Betsholtz C. Analysis of mural cell recruitment to tumor vessels. Circulation 105:112-117, 2002.
     

  19. Aase K, von Euler G, Li X, Ponten A, Thoren P, Cao R, Cao Y, Olofsson B, Gebre-Medhin S, Pekny M, Alitalo K, Betsholtz C, Eriksson U. Vascular endothelial growth factor-B-deficient mice display an atrial conduction defect. Circulation 104:358-364, 2001.
     

  20. Hellstrom M, Gerhardt H, Kalen M, Li X, Eriksson U, Wolburg H, Betsholtz C. Lack of pericytes leads to endothelial hyperplasia and abnormal vascular morphogenesis. J Cell Biol 153:543-553, 2001.
     

  21. Karlsson L, Lindahl P, Heath JK, Betsholtz C. Abnormal gastrointestinal development in PDGF-A and PDGFR-(alpha) deficient mice implicates a novel mesenchymal structure with putative instructive properties in villus morphogenesis. Development 127:3457-3466, 2000.
     

  22. Gnessi L, Basciani S, Mariani S, Arizzi M, Spera G, Wang C, Bondjers C, Karlsson L, Betsholtz C. Leydig cell loss and spermatogenic arrest in platelet-derived growth factor (PDGF)-A-deficient mice. J Cell Biol 149:1019-1026, 2000.