Integrin β1 controls VE-cadherin localization and blood vessel stability
Open accessAbstract
Angiogenic blood vessel growth requires several distinct but integrated cellular activities. Endothelial cell sprouting and proliferation lead to the expansion of the vasculature and give rise to a highly branched, immature plexus, which is subsequently reorganized into a mature and stable network. Although it is known that integrin-mediated cell–matrix interactions are indispensable for embryonic angiogenesis, little is known about the function of integrins in different steps of vascular morphogenesis. Here, by investigating the integrin β1-subunit with inducible and endothelial-specific gene targeting in the postnatal mouse retina, we show that β1 integrin promotes endothelial sprouting but is a negative regulator of proliferation. In maturing vessels, integrin β1 is indispensable for proper localization of VE-cadherin and thereby cell–cell junction integrity. The sum of our findings establishes that integrin β1 has critical functions in the growing and maturing vasculature, and is required for the formation of stable, non-leaky blood vessels. The role of integrin β1 in angiogenesis is poorly understood. Here, the authors show that integrin β1 regulates murine angiogenesis and adherens junction integrity by controlling VE-cadherin localization, myosin light chain phosphorylation and the function of the Rap1/MRCK and Rho/Rho-kinase pathways.
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α5- and β1-integrins and fibronectin are essential for vascular development.
“The α5- and β1-integrins and fibronectin are essential for vascular development (10–13).”
From Targeting β1-integrin inhibits vascular leakage in endotoxemia (2018) · cites this paper as [10]
The Abstract reports that endothelial β1 integrin is required for angiogenic sprouting and normal embryonic vascular morphogenesis. The Discussion says fibronectin binds α5β1, but also reports that targeting endothelial α5 and αv did not substantially impair embryonic angiogenesis. The paper therefore does not establish that α5 integrin and fibronectin are each essential for vascular development. (LLM, conf=0.88)
Experimental — accuracy not yet measuredβ1-integrin endothelial knockout mice develop aberrant VE-cadherin signaling, loss of claudin-5, and immature blood-brain barrier.
“Integrin dysfunction leads to BBB abnormalities, as illustrated for example by 𝛃 1-integrin endothelial knockout mice that develop aberrant VE-cadherin signaling, loss of claudin-5, and immature BBB (663).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [663]
The Itgb1 iECKO section reports altered VE-cadherin localization in knockout retinal vessels and haemorrhaging in mutant brains, supporting junctional dysfunction and a brain vascular abnormality. It mentions Claudin 5 as a staining marker but does not report its loss, and it does not establish that the blood-brain barrier is immature. (LLM, conf=0.89)
Experimental — accuracy not yet measuredIntegrin-mediated EC adhesion to the vascular basement membrane mediates vascular stability and angiogenesis.
“Collectively, integrin-mediated EC adhesion to the vascular basement membrane is known to mediate vascular stability and angiogenesis (9, 10), but less is known about the regulation of integrin-coupled EC adhesions during vascular leakage in mature vessels.”
From Targeting β1-integrin inhibits vascular leakage in endotoxemia (2018) · cites this paper as [10]
Besides the known function of endothelial β1-integrin in maintaining vessel integrity, β1-integrin plays a key role in actively promoting vascular leak, likely via fibrillar adhesions.
“the present study clearly indicates that, besides the known function of endothelial β1-integrin in maintaining vessel integrity (10), β1-integrin plays a key role in actively promoting vascular leak, likely via fibrillar adhesions.”
From Targeting β1-integrin inhibits vascular leakage in endotoxemia (2018) · cites this paper as [10]
β1-integrin continues to play a critical role in vessel integrity during postnatal life, via stabilization of VE-cadherin in the developing EC-EC junctions of newly formed vessels.
“β1-integrin continues to play a critical role in vessel integrity during postnatal life, via stabilization of VE-cadherin in the developing EC–EC junctions of newly formed vessels (10).”
From Targeting β1-integrin inhibits vascular leakage in endotoxemia (2018) · cites this paper as [10]
The α5β1-integrin heterodimer is a major endothelial fibronectin receptor.
“The α5β1-integrin heterodimer is a major endothelial fibronectin receptor.”
From Targeting β1-integrin inhibits vascular leakage in endotoxemia (2018) · cites this paper as [10]
β1-integrin is a key regulator of blood vessel development and continues to play a critical, context-dependent role in vessel sprouting and stability during postnatal life.
“β1-integrin is a key regulator of blood vessel development (11, 12), and it continues to play a critical, context-dependent role in vessel sprouting and stability during postnatal life (10).”
From Targeting β1-integrin inhibits vascular leakage in endotoxemia (2018) · cites this paper as [10]
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References 63 · Cited by 229
- Authors
- Yamamoto, H., Ehling, M., Kato, K., Kanai, K., van Lessen, M., Frye, M., Zeuschner, D., Nakayama, M., Vestweber, D., & Adams, R. H.
- Affiliations
- University of Münster (DE)
- Max Planck Institute for Molecular Biomedicine (DE)
- Corresponding author
- Adams, Ralf H.
- ORCID
- Venue
- Nature Communications
- Published
- 2015-03-10
- Volume
- 6
- Issue
- 1
- Pages
- 6429-6429
- ISSN
- 2041-1723 (ISSN-L)
- OpenAlex
- W2004351703
- Cited by
- 229
- References
- 63
- Citations by year
- 2026: 18 · 2025: 22 · 2024: 23 · 2023: 16 · 2022: 22 · 2021: 27 · 2020: 32 · 2019: 15 · 2018: 19 · 2017: 13 · 2016: 14 · 2015: 8
- FWCI
- 15.87
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Nature Communications (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft (SFB 629)
- Max-Planck-Gesellschaft
- Topics
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Keywords
- beta1 integrin, VE-cadherin, angiogenesis, blood vessel maturation, endothelial sprouting, endothelial cell proliferation, adherens junctions, myosin light chain phosphorylation, Rho/Rho-kinase pathway, vascular stability
- MeSH terms
- Cadherin 5, Animals, Brain, Endothelium, Image Processing, Computer-Assisted, Immunohistochemistry, Intercellular Junctions, Microscopy, Electron, Morphogenesis, Retinal Vessels, Blotting, Western, Antigens, CD, Cadherins, Gene Targeting, Neovascularization, Physiologic, Integrin beta1, RNA, Small Interfering, Immunoprecipitation, Cell Proliferation, Mice, Real-Time Polymerase Chain Reaction
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