The role of the cysteine-rich domain and netrin-like domain of secreted frizzled-related protein 4 in angiogenesis inhibition in vitro

Secreted frizzled-related protein 4 (sFRP4) is a Wnt signaling antagonist. Classically, sFRP4 antagonizes the canonical Wnt signaling pathway, resulting in decreased cellular proliferation and increased apoptosis. Recent research from our laboratory has established that sFRP4 inhibits angiogenesis b...

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Main Authors: Longman, D., Arfuso, F., Viola, H., Hool, L., Dharmarajan, Arunasalam
Format: Journal Article
Published: Cognizant Communication Corp. 2012
Subjects:
Online Access:http://hdl.handle.net/20.500.11937/33951
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author Longman, D.
Arfuso, F.
Viola, H.
Hool, L.
Dharmarajan, Arunasalam
author_facet Longman, D.
Arfuso, F.
Viola, H.
Hool, L.
Dharmarajan, Arunasalam
author_sort Longman, D.
building Curtin Institutional Repository
collection Online Access
description Secreted frizzled-related protein 4 (sFRP4) is a Wnt signaling antagonist. Classically, sFRP4 antagonizes the canonical Wnt signaling pathway, resulting in decreased cellular proliferation and increased apoptosis. Recent research from our laboratory has established that sFRP4 inhibits angiogenesis by decreasing proliferation, migration, and tube formation of endothelial cells. The objective of this study was to examine the role of sFRP4’s cysteine-rich domain (CRD) and netrin-like domain (NLD) in angiogenesis inhibition. Experiments were carried out to examine cell death and tube formation of endothelial cells after treatment with the CRD and the NLD. The CRD was seen to inhibit tube formation of endothelial cells, which suggests that this domain is important to sFRP4’s antiangiogenesis property. In addition, the NLD promoted endothelial cell death and may also inhibit angiogenesis. Furthermore, treatment with the CRD and the NLD increased endothelial intracellular calcium levels. Our findings implicate a role for both the CRD and NLD in angiogenesis inhibition by sFRP4. It is suggestive of alternative antiangiogenic downstream targets of canonical Wnt signaling and a possible importance of the noncanonical Ca2+ Wnt signaling pathway in sFRP4-mediated angiogenesis inhibition.
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publishDate 2012
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spelling curtin-20.500.11937-339512017-09-13T15:55:20Z The role of the cysteine-rich domain and netrin-like domain of secreted frizzled-related protein 4 in angiogenesis inhibition in vitro Longman, D. Arfuso, F. Viola, H. Hool, L. Dharmarajan, Arunasalam Secreted firzzled-related protein 4 (sFRP4) Apoptosis Calcium signaling Angiogenesis Secreted frizzled-related protein 4 (sFRP4) is a Wnt signaling antagonist. Classically, sFRP4 antagonizes the canonical Wnt signaling pathway, resulting in decreased cellular proliferation and increased apoptosis. Recent research from our laboratory has established that sFRP4 inhibits angiogenesis by decreasing proliferation, migration, and tube formation of endothelial cells. The objective of this study was to examine the role of sFRP4’s cysteine-rich domain (CRD) and netrin-like domain (NLD) in angiogenesis inhibition. Experiments were carried out to examine cell death and tube formation of endothelial cells after treatment with the CRD and the NLD. The CRD was seen to inhibit tube formation of endothelial cells, which suggests that this domain is important to sFRP4’s antiangiogenesis property. In addition, the NLD promoted endothelial cell death and may also inhibit angiogenesis. Furthermore, treatment with the CRD and the NLD increased endothelial intracellular calcium levels. Our findings implicate a role for both the CRD and NLD in angiogenesis inhibition by sFRP4. It is suggestive of alternative antiangiogenic downstream targets of canonical Wnt signaling and a possible importance of the noncanonical Ca2+ Wnt signaling pathway in sFRP4-mediated angiogenesis inhibition. 2012 Journal Article http://hdl.handle.net/20.500.11937/33951 10.3727/096504012X13425470196010 Cognizant Communication Corp. fulltext
spellingShingle Secreted firzzled-related protein 4 (sFRP4)
Apoptosis
Calcium signaling
Angiogenesis
Longman, D.
Arfuso, F.
Viola, H.
Hool, L.
Dharmarajan, Arunasalam
The role of the cysteine-rich domain and netrin-like domain of secreted frizzled-related protein 4 in angiogenesis inhibition in vitro
title The role of the cysteine-rich domain and netrin-like domain of secreted frizzled-related protein 4 in angiogenesis inhibition in vitro
title_full The role of the cysteine-rich domain and netrin-like domain of secreted frizzled-related protein 4 in angiogenesis inhibition in vitro
title_fullStr The role of the cysteine-rich domain and netrin-like domain of secreted frizzled-related protein 4 in angiogenesis inhibition in vitro
title_full_unstemmed The role of the cysteine-rich domain and netrin-like domain of secreted frizzled-related protein 4 in angiogenesis inhibition in vitro
title_short The role of the cysteine-rich domain and netrin-like domain of secreted frizzled-related protein 4 in angiogenesis inhibition in vitro
title_sort role of the cysteine-rich domain and netrin-like domain of secreted frizzled-related protein 4 in angiogenesis inhibition in vitro
topic Secreted firzzled-related protein 4 (sFRP4)
Apoptosis
Calcium signaling
Angiogenesis
url http://hdl.handle.net/20.500.11937/33951