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Alternative Splicing in Angiogenesis

Elizabeth Bowler1, Sebastian Oltean2

  • 1Institute of Biomedical and Clinical Sciences, Medical School, College of Medicine and Health, University of Exeter, Exeter EX4 4PY, UK. e.bowler@exeter.ac.uk.

International Journal of Molecular Sciences
|April 28, 2019
PubMed

Insights

Alternative splicing generates diverse protein variants, including those that regulate or inhibit key biological processes like angiogenesis. This review examines splice isoforms of critical angiogenesis genes.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • Alternative splicing of pre-messenger RNA (mRNA) generates multiple splice isoforms from a single gene, leading to proteins with distinct or even opposing functions.
  • This isoform diversity adds a regulatory layer to cellular processes, with some splice variants acting as inhibitors of canonical protein functions.
  • Angiogenesis, the formation of new blood vessels, is a complex process significantly influenced by alternative splicing mechanisms.

Purpose of the Study:

  • To review the role of alternative splicing in regulating angiogenesis.
  • To focus on the alternative spliced isoforms of key genes central to the angiogenesis process.

Main Methods:

  • Literature review of scientific articles focusing on alternative splicing and angiogenesis.
  • Analysis of key genes involved in angiogenesis, including their splice isoforms.

Main Results:

  • Alternative splicing generates functionally distinct isoforms for critical angiogenesis genes.
  • These isoforms can modulate the canonical functions of proteins involved in blood vessel formation.
  • Specific genes examined include Vascular Endothelial Growth Factor-A (VEGF-A), its receptors (VEGFR1, VEGFR2), Neuropilin-1 (NRP-1), Fibroblast Growth Factor Receptors (FGFRs), Vasohibin-1, Vasohibin-2, Hypoxia-Inducible Factor-1 alpha (HIF-1α), Angiopoietin-1, and Angiopoietin-2.

Conclusions:

  • Alternative splicing is a crucial regulatory mechanism in angiogenesis.
  • Understanding the diverse functions of splice isoforms is essential for comprehending blood vessel development and related pathologies.
  • Targeting specific splice isoforms may offer novel therapeutic strategies for angiogenesis-related diseases.
Keywords:
FGFRHIF-1NRPVEGFVEGFRalternative splicingangiogenesisangiopoietinvasohibin

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