Lipocalin-7 is a matricellular regulator of angiogenesis.
<h4>Background</h4>Matricellular proteins are extracellular regulators of cellular adhesion, signaling and performing a variety of physiological behaviors such as proliferation, migration and differentiation. Within vascular microenvironments, matricellular proteins exert both positive a...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2010-11-01
|
| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0013905&type=printable |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849734953371172864 |
|---|---|
| author | Leslie J Brown Mariam Alawoki Mary E Crawford Tiffany Reida Allison Sears Tory Torma Allan R Albig |
| author_facet | Leslie J Brown Mariam Alawoki Mary E Crawford Tiffany Reida Allison Sears Tory Torma Allan R Albig |
| author_sort | Leslie J Brown |
| collection | DOAJ |
| description | <h4>Background</h4>Matricellular proteins are extracellular regulators of cellular adhesion, signaling and performing a variety of physiological behaviors such as proliferation, migration and differentiation. Within vascular microenvironments, matricellular proteins exert both positive and negative regulatory cues to vascular endothelium. The relative balance of these matricellular cues is believed to be critical for vascular homeostasis, angiogenesis activation or angiogenesis resolution. However, our knowledge of matricellular proteins within vascular microenvironments and the mechanisms by which these proteins impact vascular function remain largely undefined. The matricellular protein lipocalin-7 (LCN7) is found throughout vascular microenvironments, and circumstantial evidence suggests that LCN7 may be an important regulator of angiogenesis. Therefore, we hypothesized that LCN7 may be an important regulator of vascular function.<h4>Methodology and principal findings</h4>To test this hypothesis, we examined the effect of LCN7 overexpression, recombinant protein and gene knockdown in a series of in vitro and in vivo models of angiogenesis. We found that overexpression of LCN7 in MB114 and SVEC murine endothelial cell lines or administration of highly purified recombinant LCN7 protein increased endothelial cell invasion. Similarly, LCN7 increased angiogenic sprouting from quiescent endothelial cell monolayers and ex vivo aortic rings. Moreover, LCN7 increased endothelial cell sensitivity to TGF-β but did not affect sensitivity to other pro-angiogenic growth factors including bFGF and VEGF. Finally, morpholino based knockdown of LCN7 in zebrafish embryos specifically inhibited angiogenic sprouting but did not affect vasculogenesis within injected embryos.<h4>Conclusions and significance</h4>No functional analysis has previously been performed to elucidate the function of LCN7 in vascular or other cellular processes. Collectively, our results show for the first time that LCN7 is an important pro-angiogenic matricellular protein of vascular microenvironments. |
| format | Article |
| id | doaj-art-8b0a08090b9d46648243cbb3ade7d75f |
| institution | DOAJ |
| issn | 1932-6203 |
| language | English |
| publishDate | 2010-11-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-8b0a08090b9d46648243cbb3ade7d75f2025-08-20T03:07:40ZengPublic Library of Science (PLoS)PLoS ONE1932-62032010-11-01511e1390510.1371/journal.pone.0013905Lipocalin-7 is a matricellular regulator of angiogenesis.Leslie J BrownMariam AlawokiMary E CrawfordTiffany ReidaAllison SearsTory TormaAllan R Albig<h4>Background</h4>Matricellular proteins are extracellular regulators of cellular adhesion, signaling and performing a variety of physiological behaviors such as proliferation, migration and differentiation. Within vascular microenvironments, matricellular proteins exert both positive and negative regulatory cues to vascular endothelium. The relative balance of these matricellular cues is believed to be critical for vascular homeostasis, angiogenesis activation or angiogenesis resolution. However, our knowledge of matricellular proteins within vascular microenvironments and the mechanisms by which these proteins impact vascular function remain largely undefined. The matricellular protein lipocalin-7 (LCN7) is found throughout vascular microenvironments, and circumstantial evidence suggests that LCN7 may be an important regulator of angiogenesis. Therefore, we hypothesized that LCN7 may be an important regulator of vascular function.<h4>Methodology and principal findings</h4>To test this hypothesis, we examined the effect of LCN7 overexpression, recombinant protein and gene knockdown in a series of in vitro and in vivo models of angiogenesis. We found that overexpression of LCN7 in MB114 and SVEC murine endothelial cell lines or administration of highly purified recombinant LCN7 protein increased endothelial cell invasion. Similarly, LCN7 increased angiogenic sprouting from quiescent endothelial cell monolayers and ex vivo aortic rings. Moreover, LCN7 increased endothelial cell sensitivity to TGF-β but did not affect sensitivity to other pro-angiogenic growth factors including bFGF and VEGF. Finally, morpholino based knockdown of LCN7 in zebrafish embryos specifically inhibited angiogenic sprouting but did not affect vasculogenesis within injected embryos.<h4>Conclusions and significance</h4>No functional analysis has previously been performed to elucidate the function of LCN7 in vascular or other cellular processes. Collectively, our results show for the first time that LCN7 is an important pro-angiogenic matricellular protein of vascular microenvironments.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0013905&type=printable |
| spellingShingle | Leslie J Brown Mariam Alawoki Mary E Crawford Tiffany Reida Allison Sears Tory Torma Allan R Albig Lipocalin-7 is a matricellular regulator of angiogenesis. PLoS ONE |
| title | Lipocalin-7 is a matricellular regulator of angiogenesis. |
| title_full | Lipocalin-7 is a matricellular regulator of angiogenesis. |
| title_fullStr | Lipocalin-7 is a matricellular regulator of angiogenesis. |
| title_full_unstemmed | Lipocalin-7 is a matricellular regulator of angiogenesis. |
| title_short | Lipocalin-7 is a matricellular regulator of angiogenesis. |
| title_sort | lipocalin 7 is a matricellular regulator of angiogenesis |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0013905&type=printable |
| work_keys_str_mv | AT lesliejbrown lipocalin7isamatricellularregulatorofangiogenesis AT mariamalawoki lipocalin7isamatricellularregulatorofangiogenesis AT maryecrawford lipocalin7isamatricellularregulatorofangiogenesis AT tiffanyreida lipocalin7isamatricellularregulatorofangiogenesis AT allisonsears lipocalin7isamatricellularregulatorofangiogenesis AT torytorma lipocalin7isamatricellularregulatorofangiogenesis AT allanralbig lipocalin7isamatricellularregulatorofangiogenesis |