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An IP-10 (CXCL10)-derived peptide inhibits angiogenesis

Yates-Binder, CC and Rodgers, M and Jaynes, J and Wells, A and Bodnar, RJ and Turner, T (2012) An IP-10 (CXCL10)-derived peptide inhibits angiogenesis. PLoS ONE, 7 (7).

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Abstract

Angiogenesis plays a critical role in processes such as organ development, wound healing, and tumor growth. It requires well-orchestrated integration of soluble and matrix factors and timely recognition of such signals to regulate this process. Previous work has shown that newly forming vessels express the chemokine receptor CXC receptor 3 (CXCR3) and, activation by its ligand IP-10 (CXCL10), both inhibits development of new vasculature and causes regression of newly formed vessels. To identify and develop new therapeutic agents to limit or reverse pathological angiogenesis, we identified a 21 amino acid fragment of IP-10, spanning the α-helical domain residues 77-98, that mimic the actions of the whole IP-10 molecule on endothelial cells. Treatment of the endothelial cells with the 22 amino acid fragment referred to as IP-10p significantly inhibited VEGF-induced endothelial motility and tube formation in vitro, properties critical for angiogenesis. Using a Matrigel plug assay in vivo, we demonstrate that IP-10p both prevented vessel formation and induced involution of nascent vessels. CXCR3 neutralizing antibody was able to block the inhibitory effects of the IP-10p, demonstrating specificity of the peptide. Inhibition of endothelial function by IP-10p was similar to that described for IP-10, secondary to CXCR3-mediated increase in cAMP production, activation of PKA inhibiting cell migration, and inhibition of VEGF-mediated m-calpain activation. IP-10p provides a novel therapeutic agent that inhibits endothelial cell function thus, allowing for the modulation of angiogenesis. © 2012 Yates-Binder et al.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Yates-Binder, CCcecelia.yates@pitt.eduCEY4
Rodgers, M
Jaynes, J
Wells, Aahw6@pitt.eduAHW6
Bodnar, RJrcdbdnr@pitt.eduRCDBDNR
Turner, T
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorProost, PaulUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Date: 16 July 2012
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 7
Number: 7
DOI or Unique Handle: 10.1371/journal.pone.0040812
Schools and Programs: School of Medicine > Pathology
Refereed: Yes
Other ID: NLM PMC3397949
PubMed Central ID: PMC3397949
PubMed ID: 22815829
Date Deposited: 05 Oct 2012 19:09
Last Modified: 30 Oct 2018 14:00
URI: http://d-scholarship.pitt.edu/id/eprint/15589

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