β1 Integrin Establishes Endothelial Cell Polarity and Arteriolar Lumen Formation via a Par3-Dependent Mechanism
Open accessAbstract
Maintenance of single-layered endothelium, squamous endothelial cell shape, and formation of a patent vascular lumen all require defined endothelial cell polarity. Loss of beta1 integrin (Itgb1) in nascent endothelium leads to disruption of arterial endothelial cell polarity and lumen formation. The loss of polarity is manifested as cuboidal-shaped endothelial cells with dysregulated levels and mislocalization of normally polarized cell-cell adhesion molecules, as well as decreased expression of the polarity gene Par3 (pard3). beta1 integrin and Par3 are both localized to the endothelial layer, with preferential expression of Par3 in arterial endothelium. Luminal occlusion is also exclusively noted in arteries, and is partially rescued by replacement of Par3 protein in beta1-deficient vessels. Combined, our findings demonstrate that beta1 integrin functions upstream of Par3 as part of a molecular cascade required for endothelial cell polarity and lumen formation.
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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 [12]
The Results section ('β1 integrin loss results in dose-dependent lethality'; page not provided) reports embryonic death and vascular rupture after endothelial β1-integrin deletion, supporting its importance in vascular development. The Introduction says α5β1 is implicated in vascular morphogenesis but does not establish that α5 is essential; our copy does not establish that fibronectin is essential either. (LLM, conf=0.88)
Experimental — accuracy not yet measuredThe 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 [12]
The Introduction (page unavailable) identifies α5β1 as an endothelial integrin and describes integrins generally as extracellular-matrix receptors. It does not identify fibronectin as α5β1’s ligand or say that α5β1 is a major endothelial fibronectin receptor; searches for “fibronectin” and “α5β1” found no passage establishing those points. (LLM, conf=0.85)
Experimental — accuracy not yet measuredDuring embryonic development, β1-integrin regulates vascular sprouting and vessel lumen formation.
“During embryonic development, β1-integrin regulates vascular sprouting and vessel lumen formation (11, 12).”
From Targeting β1-integrin inhibits vascular leakage in endotoxemia (2018) · cites this paper as [12]
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 [12]
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- Authors
- Zovein, A. C., Luque, A., Turlo, K. A., Hofmann, J. J., Yee, K. M., Becker, M. S., Fassler, R., Mellman, I., Lane, T. F., & Iruela-Arispe, M. L.
- Affiliations
- University of California, Los Angeles (US)
- Genentech (US)
- Venue
- Developmental Cell
- Publisher
- Elsevier BV
- Published
- 2010-01
- Volume
- 18
- Issue
- 1
- Pages
- 39-51
- ISSN
- 1534-5807 (ISSN-L)
- PMC
- PMC3178410
- OpenAlex
- W2125764697
- Cited by
- 256
- References
- 41
- Citations by year
- 2026: 4 · 2025: 11 · 2024: 11 · 2023: 8 · 2022: 19 · 2021: 12 · 2020: 10 · 2019: 12 · 2018: 16 · 2017: 18 · 2016: 14 · 2015: 21 · 2014: 17 · 2013: 23 · 2012: 20
- FWCI
- 18.86
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Developmental Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- Funders
- National Institutes of Health
- National Heart, Lung, and Blood Institute (R01HL085618, HL085618)
- National Cancer Institute (R01CA126935, CA126935)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (K-12-HD 00850, K12HD000850)
- Topics
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- beta1 integrin, endothelial cell polarity, Par3, cell-cell adhesion, endothelial cell morphology, luminal occlusion, vascular lumen
- MeSH terms
- Animals, Arterioles, Cell Adhesion, Cell Differentiation, Disease Models, Animal, Signal Transduction, Cell Adhesion Molecules, Cell Polarity, Mice, Knockout, Gene Expression Regulation, Developmental, Cell Cycle Proteins, Neovascularization, Physiologic, Integrin beta1, Endothelial Cells, Cell Shape, Adaptor Proteins, Signal Transducing, Mice
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