Peptides derived from the integrin β cytoplasmic tails inhibit angiogenesis
Abstract Background Integrins are essential regulators of angiogenesis. However, the antiangiogenic potential of peptides derived from the integrin cytoplasmic tails (CT) remains mostly undetermined. Methods Here we designed a panel of membrane-penetrating peptides (termed as mβCTPs), each comprisin...
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doaj-26d4184c31ae454a8ff685ec29680ccc2020-11-25T00:12:29ZengBMCCell Communication and Signaling1478-811X2018-07-0116111510.1186/s12964-018-0248-8Peptides derived from the integrin β cytoplasmic tails inhibit angiogenesisZhongyuan Cao0Xinfeng Suo1Yudan Chu2Zhou Xu3Yun Bao4Chunxiao Miao5Wenfeng Deng6Kaijun Mao7Juan Gao8Zhen Xu9Yan-Qing Ma10School of Environmental and Chemical Engineering, Shanghai UniversitySchool of Life Sciences, Shanghai UniversitySchool of Life Sciences, Shanghai UniversitySchool of Life Sciences, Shanghai UniversitySchool of Life Sciences, Shanghai UniversitySchool of Life Sciences, Shanghai UniversitySchool of Life Sciences, Shanghai UniversitySchool of Life Sciences, Shanghai UniversitySchool of Life Sciences, Shanghai UniversitySchool of Life Sciences, Shanghai UniversitySchool of Environmental and Chemical Engineering, Shanghai UniversityAbstract Background Integrins are essential regulators of angiogenesis. However, the antiangiogenic potential of peptides derived from the integrin cytoplasmic tails (CT) remains mostly undetermined. Methods Here we designed a panel of membrane-penetrating peptides (termed as mβCTPs), each comprising a C-terminal NxxY motif from one of the conserved integrin β CTs, and evaluated their antiangiogenic ability using both in vitro and in vivo approaches. Results We found that mβ3CTP, mβ5CTP and mβ6CTP, derived respectively from the integrin β3, β5 and β6 CTs, but not others, exhibit antiangiogenic ability. Interestingly, we observed that the integrin β3, β5 and β6 CTs but not others are able to interact with β3-endonexin. In addition, the antiangiogenic core in mβ3CTP is identical to a previously identified β3-endonexin binding region in the integrin β3 CT, indicating that the antiangiogenic mβCTPs may function via their binding to β3-endonexin. Consistently, knockdown of endogenous β3-endonexin in HUVECs significantly suppresses tube formation, suggesting that β3-endonexin is proangiogenic. However, neither treatment with the antiangiogenic mβCTPs nor knockdown of endogenous β3-endonexin affects integrin-mediated HUVEC adhesion and migration, indicating that their antiangiogenic effect may not rely on directly regulating integrin activity. Importantly, both treatment with the antiangiogenic mβCTPs and knockdown of endogenous β3-endonexin in HUVECs inhibit VEGF expression and cell proliferation, thereby providing mechanistic explanations for the functional consequences. Conclusion Our results suggest that the antiangiogenic mβCTPs can interact with β3-endonexin in vascular endothelial cells and suppress its function in regulating VEGF expression and cell proliferation, thus disclosing a unique pathway that may be useful for developing novel antiangiogenic strategies.http://link.springer.com/article/10.1186/s12964-018-0248-8AngiogenesisEndothelial cellsIntegrinsCytoplasmic tailsβ3-endonexin |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Zhongyuan Cao Xinfeng Suo Yudan Chu Zhou Xu Yun Bao Chunxiao Miao Wenfeng Deng Kaijun Mao Juan Gao Zhen Xu Yan-Qing Ma |
spellingShingle |
Zhongyuan Cao Xinfeng Suo Yudan Chu Zhou Xu Yun Bao Chunxiao Miao Wenfeng Deng Kaijun Mao Juan Gao Zhen Xu Yan-Qing Ma Peptides derived from the integrin β cytoplasmic tails inhibit angiogenesis Cell Communication and Signaling Angiogenesis Endothelial cells Integrins Cytoplasmic tails β3-endonexin |
author_facet |
Zhongyuan Cao Xinfeng Suo Yudan Chu Zhou Xu Yun Bao Chunxiao Miao Wenfeng Deng Kaijun Mao Juan Gao Zhen Xu Yan-Qing Ma |
author_sort |
Zhongyuan Cao |
title |
Peptides derived from the integrin β cytoplasmic tails inhibit angiogenesis |
title_short |
Peptides derived from the integrin β cytoplasmic tails inhibit angiogenesis |
title_full |
Peptides derived from the integrin β cytoplasmic tails inhibit angiogenesis |
title_fullStr |
Peptides derived from the integrin β cytoplasmic tails inhibit angiogenesis |
title_full_unstemmed |
Peptides derived from the integrin β cytoplasmic tails inhibit angiogenesis |
title_sort |
peptides derived from the integrin β cytoplasmic tails inhibit angiogenesis |
publisher |
BMC |
series |
Cell Communication and Signaling |
issn |
1478-811X |
publishDate |
2018-07-01 |
description |
Abstract Background Integrins are essential regulators of angiogenesis. However, the antiangiogenic potential of peptides derived from the integrin cytoplasmic tails (CT) remains mostly undetermined. Methods Here we designed a panel of membrane-penetrating peptides (termed as mβCTPs), each comprising a C-terminal NxxY motif from one of the conserved integrin β CTs, and evaluated their antiangiogenic ability using both in vitro and in vivo approaches. Results We found that mβ3CTP, mβ5CTP and mβ6CTP, derived respectively from the integrin β3, β5 and β6 CTs, but not others, exhibit antiangiogenic ability. Interestingly, we observed that the integrin β3, β5 and β6 CTs but not others are able to interact with β3-endonexin. In addition, the antiangiogenic core in mβ3CTP is identical to a previously identified β3-endonexin binding region in the integrin β3 CT, indicating that the antiangiogenic mβCTPs may function via their binding to β3-endonexin. Consistently, knockdown of endogenous β3-endonexin in HUVECs significantly suppresses tube formation, suggesting that β3-endonexin is proangiogenic. However, neither treatment with the antiangiogenic mβCTPs nor knockdown of endogenous β3-endonexin affects integrin-mediated HUVEC adhesion and migration, indicating that their antiangiogenic effect may not rely on directly regulating integrin activity. Importantly, both treatment with the antiangiogenic mβCTPs and knockdown of endogenous β3-endonexin in HUVECs inhibit VEGF expression and cell proliferation, thereby providing mechanistic explanations for the functional consequences. Conclusion Our results suggest that the antiangiogenic mβCTPs can interact with β3-endonexin in vascular endothelial cells and suppress its function in regulating VEGF expression and cell proliferation, thus disclosing a unique pathway that may be useful for developing novel antiangiogenic strategies. |
topic |
Angiogenesis Endothelial cells Integrins Cytoplasmic tails β3-endonexin |
url |
http://link.springer.com/article/10.1186/s12964-018-0248-8 |
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