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 journalArticle

52 Citations (Scopus)

Abstract

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
Volume79
Issue number1
DOIs
StatePublished - Jan 1 2010

Fingerprint

Semaphorins
Endothelial cells
Cell proliferation
Cell Movement
Endothelial Cells
Cell Proliferation
Apoptosis
Blood Vessels
Genes
Matrix Metalloproteinase 9
Blood vessels
Protein-Tyrosine Kinases
Extracellular Matrix
Axons
Assays
Chemical activation
Degradation
Molecules

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Cardiology and Cardiovascular Medicine
  • Cell Biology

Cite this

Semaphorin 5A promotes angiogenesis by increasing endothelial cell proliferation, migration, and decreasing apoptosis. / Sadanandam, Anguraj; Rosenbaugh, Erin G.; Singh, Seema; Varney, Michelle; Singh, Rakesh K.

In: Microvascular Research, Vol. 79, No. 1, 01.01.2010, p. 1-9.

Research output: Contribution to journalArticle

Sadanandam, Anguraj ; Rosenbaugh, Erin G. ; Singh, Seema ; Varney, Michelle ; Singh, Rakesh K. / Semaphorin 5A promotes angiogenesis by increasing endothelial cell proliferation, migration, and decreasing apoptosis. In: Microvascular Research. 2010 ; Vol. 79, No. 1. pp. 1-9.
@article{8dfa3478a80448c89873ab294f9c0aad,
title = "Semaphorin 5A promotes angiogenesis by increasing endothelial cell proliferation, migration, and decreasing apoptosis",
abstract = "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.",
keywords = "Akt phosphorylation, Angiogenesis, Endothelial cells, Matrix metalloproteinase, Met receptor, Migration, Proliferation, Sema5A, Semaphorin",
author = "Anguraj Sadanandam and Rosenbaugh, {Erin G.} and Seema Singh and Michelle Varney and Singh, {Rakesh K}",
year = "2010",
month = "1",
day = "1",
doi = "10.1016/j.mvr.2009.10.005",
language = "English (US)",
volume = "79",
pages = "1--9",
journal = "Microvascular Research",
issn = "0026-2862",
publisher = "Academic Press Inc.",
number = "1",

}

TY - JOUR

T1 - Semaphorin 5A promotes angiogenesis by increasing endothelial cell proliferation, migration, and decreasing apoptosis

AU - Sadanandam, Anguraj

AU - Rosenbaugh, Erin G.

AU - Singh, Seema

AU - Varney, Michelle

AU - Singh, Rakesh K

PY - 2010/1/1

Y1 - 2010/1/1

N2 - 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.

AB - 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.

KW - Akt phosphorylation

KW - Angiogenesis

KW - Endothelial cells

KW - Matrix metalloproteinase

KW - Met receptor

KW - Migration

KW - Proliferation

KW - Sema5A

KW - Semaphorin

UR - http://www.scopus.com/inward/record.url?scp=73449115295&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=73449115295&partnerID=8YFLogxK

U2 - 10.1016/j.mvr.2009.10.005

DO - 10.1016/j.mvr.2009.10.005

M3 - Article

C2 - 19850054

AN - SCOPUS:73449115295

VL - 79

SP - 1

EP - 9

JO - Microvascular Research

JF - Microvascular Research

SN - 0026-2862

IS - 1

ER -