An IP-10 (CXCL10)-Derived Peptide Inhibits Angiogenesis

Yates-Binder, Cecelia C; Rodgers, Margaret E.; Jaynes, Jesse M.; Wells, Alan; Bodnar, Richard J.; Turner, Timothy

doi:10.1371/journal.pone.0040812

Cited by 71 publications

(68 citation statements)

References 24 publications

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“…However, we were unable to directly show either the effect of CXCR3 on VSMC migration or the effect of CXCL10 on HUVEC migration. Yates-Binder et al 24 already showed an inhibiting effect of an interferon-inducible protein 10 peptide on endothelial cell motility and tube formation, although showing this in a different cell type (human microvascular endothelial cells versus HUVECs).…”

Section: Discussionmentioning

confidence: 99%

Absence of Chemokine (C-X-C Motif) Ligand 10 Diminishes Perfusion Recovery After Local Arterial Occlusion in Mice

Borne¹,

Haverslag²,

Brandt³

et al. 2014

ATVB

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Objective— In arteriogenesis, pre-existing anastomoses undergo enlargement to restore blood flow in ischemic tissues. Chemokine (C-X-C motif) ligand 10 (CXCL10) is secreted after Toll-like receptor activation. Toll-like receptors are involved in arteriogenesis; however, the role of CXCL10 is still unclear. In this study, we investigated the role for CXCL10 in a murine hindlimb ischemia model. Approach and Results— Unilateral femoral artery ligation was performed in wild-type (WT) and CXCL10 −/− knockout (KO) mice and perfusion recovery was measured using laser-Doppler perfusion analysis. Perfusion recovery was significantly lower in KO mice compared with WT at days 4 and 7 after surgery (KO versus WT: 28±5% versus 81±13% at day 4; P =0.003 and 57±12% versus 107±8% at day 7; P =0.003). Vessel measurements of α-smooth muscle actin–positive vessels revealed increasing numbers in time after surgery, which was significantly higher in WT when compared with that in KO. Furthermore, α-smooth muscle actin–positive vessels were significantly larger in WT when compared with those in KO at day 7 (wall thickness, P <0.001; lumen area, P =0.003). Local inflammation was assessed in hindlimb muscles, but this did not differ between WT and KO. Chimerization experiments analyzing perfusion recovery and histology revealed an equal contribution for bone marrow–derived and circulating CXCL10. Migration assays showed a stimulating role for both intrinsic and extrinsic CXCL10 in vascular smooth muscle cell migration. Conclusions— CXCL10 plays a causal role in arteriogenesis. Bone marrow–derived CXCL10 and tissue-derived CXCL10 play a critical role in accelerating perfusion recovery after arterial occlusion in mice probably by promoting vascular smooth muscle cell recruitment and maturation of pre-existing anastomoses.

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Section: Discussionmentioning

confidence: 99%

Absence of Chemokine (C-X-C Motif) Ligand 10 Diminishes Perfusion Recovery After Local Arterial Occlusion in Mice

Borne¹,

Haverslag²,

Brandt³

et al. 2014

ATVB

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“…Thus, CXCL10, via derived peptide [70], or AAV-CXCL10 vector can be topically applied to the ocular surface to reduce or prevent corneal angiogenesis associated with chemical injury and graft rejection, the latter of which is related to corneal lymphangiogenesis [7, 71]. …”

Section: Discussionmentioning

confidence: 99%

CXCL10 suppression of hem- and lymph-angiogenesis in inflamed corneas through MMP13

Gao

Liu

et al. 2017

Angiogenesis

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Though not present in the normal adult cornea, both hem- and lymph-angiogenesis can be induced in this tissue after an inflammatory, infectious, or traumatic insult. We previously showed that the chemokine CXCL10 plays a key role in eradicating invading Candida (C.) albicans in C57BL6 mouse corneas. However, even after the clearance of pathogens, infection-induced inflammation and angiogenesis continue to progress in the cornea. The aim of this study is define the role of CXCL10 as a major angiostatic factor in modulating cornea angiogenesis in B6 mouse corneas under pathogenic conditions. We showed that epithelial expression of CXCL10, driven by AAV9 vector, suppressed both infection- and inflammation-induced hem and lymph angiogenesis, whereas the neutralization of CXCL10 as well as its receptor CXCR3 greatly promoted these processes. The inhibitory effect of CXCL10 was unrelated to its antimicrobial activity, but through the suppression of the expression of many angiogenic factors, including VEGFa and c, and MMP-13 in vivo. Inhibition of MMP13 but not TIMPs, attenuated suture-induced neovascularization but had no effects on CXCL10 expression. Strikingly, topical application of CXCL10 post-C. albicans infection effectively blocked both hem- and lymph-angiogenesis and preserved the integrity of sensory nerves in the cornea. Taken together, CXCL10 has strong inhibitory effects on neovascularization, whereas MMP13 is required for neovascularization in C. albicans-infected corneas and the local application of CXCL10 or MMP13 inhibitors, alone or as adjuvant therapy, may target hem- and lymph-angiogenesis in the inflamed corneas.

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“…IP‐10, a DPP IV/CD26 substrate inactivated by its proteolytic activity, is a chemotactic proinflammatory cytokine and chemoattractant for monocytes and T lymphocytes with the ability to inhibit the proliferation of endothelial cells . It has been shown that IP‐10 inhibits angiogenesis and delays reepithelialization of wounds .…”

Section: Discussionmentioning

confidence: 99%

Involvement of DPP IV/CD26 in cutaneous wound healing process in mice

Batičić

Pugel

Detel

et al. 2017

Wound Repair Regeneration

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Dipeptidyl peptidase IV (DPP IV/CD26) is a widely distributed multifunctional protein that plays a significant role in different physiological as well as pathological processes having a broad spectrum of bioactive substrates and immunomodulative properties. It has potential influence on different processes crucial for wound healing, including cell adhesion, migration, apoptosis, and extracellular matrix degradation. However, despite its known enzymatic and immunomodulative functions, limited data characterize the role of DPP IV/CD26 in cutaneous wound healing mechanisms. The aim of this study was to investigate the process of wound healing in conditions of CD26 deficiency in order to obtain better insights on the role of DPP IV/CD26 in cutaneous regeneration. Experimental wounds were made on the dorsal part of CD26 deficient (CD26 ) and wild-type mice (C57BL/6). The process of cutaneous wound healing was monitored on defined time schedule postwounding by macroscopic, microscopic, and biochemical analyses. Obtained results revealed a better rate of wound closure, revascularization and cell proliferation in CD26 mice, with enhanced local expression of hypoxia-inducible factor 1α and vascular endothelial growth factor. CD26 deficiency induced prompt macrophage recruitment at the site of skin damage but did not influence mobilization of T-cells in comparison with wild-type mice. CD26 mice have significantly higher values of IP-10 in serum and control skins compared with wild-type mice but values in wounds did not differ significantly on days 2, 4, and 7 of wound healing. DPP IV/CD26 activity was found to be decreased 4 days postwounding in serum and 2, 4, and 7 days postwounding in wounds of wild-type animals compared with control skins. These findings contribute to better understanding of wound healing mechanisms and could give a support in finding new therapeutic approaches for wound healing and tissue regeneration.

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An IP-10 (CXCL10)-Derived Peptide Inhibits Angiogenesis

Cited by 71 publications

References 24 publications

Absence of Chemokine (C-X-C Motif) Ligand 10 Diminishes Perfusion Recovery After Local Arterial Occlusion in Mice

Absence of Chemokine (C-X-C Motif) Ligand 10 Diminishes Perfusion Recovery After Local Arterial Occlusion in Mice

CXCL10 suppression of hem- and lymph-angiogenesis in inflamed corneas through MMP13

Involvement of DPP IV/CD26 in cutaneous wound healing process in mice

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