Semaphorin 5A promotes angiogenesis by increasing endothelial cell proliferation, migration, and decreasing apoptosis

Anguraj Sadanandam, Erin G. Rosenbaugh, Seema Singh, Michelle Varney, Rakesh K. Singh

Research output: Contribution to journalArticlepeer-review

75 Scopus citations


Semaphorin 5A (mouse, Sema5A; human, SEMA5A), is an axon regulator molecule and plays major roles during neuronal and vascular development. The importance of Sema5A during vasculogenesis, however, is unclear. The fact that Sema5A deficient mice display a defective branching of cranial vasculature supports its participation in blood vessel formation. In this study, we tested our hypothesis that Sema5A regulates angiogenesis by modulating various steps during angiogenesis. Accordingly, we demonstrated that the treatment of immortalized endothelial cells with recombinant extracellular domain of mouse Sema5A significantly increased endothelial cell proliferation and migration and decreased apoptosis. We also observed a relative increase of endothelial expression of anti-apoptotic genes relative to pro-apoptotic genes in Sema5A-treated endothelial cells suggesting its role in inhibition of apoptosis. In addition, our data suggest that Sema5A decreases apoptosis through activation of Akt, increases migration through activating Met tyrosine kinases and extracellular matrix degradation through matrix metalloproteinase 9. Moreover, in vivo Matrigel plug assays demonstrated that Sema5A induces endothelial cell migration from pre-existing vessels. In conclusion, the present work shows the pro-angiogenic role of Sema5A and provides clues on the signaling pathways that underlie them.

Original languageEnglish (US)
Pages (from-to)1-9
Number of pages9
JournalMicrovascular Research
Issue number1
StatePublished - Jan 2010


  • Akt phosphorylation
  • Angiogenesis
  • Endothelial cells
  • Matrix metalloproteinase
  • Met receptor
  • Migration
  • Proliferation
  • Sema5A
  • Semaphorin

ASJC Scopus subject areas

  • Biochemistry
  • Cardiology and Cardiovascular Medicine
  • Cell Biology


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