Vascular endothelial cell adhesion and spreading promoted by the peptide REDV of the IIICS region of plasma fibronectin is mediated by integrin alpha 4 beta 1.
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We have recently reported the attachment and spreading of human umbilical vein endothelial cells (HUVECs) upon substrates containing covalently grafted Arg-Glu-Asp-Val (REDV) peptide (Hubbell, J. A., Massia, S. P., Desai, N. P., and Drumheller, P. D. (1991) Bio/Technology 9, 568-572). This peptide has been reported to be the minimal active sequence within the CS5 site of the alternatively spliced type III connecting segment (IIICS) region of fibronectin, and the integrin alpha 4 beta 1 has been identified as the receptor on melanoma cells for this site. The integrin alpha 4 beta 1 has also been identified as the receptor for the CS1 site in the IIICS region on cells of neural crest origin, melanoma cells, lymphocytes, and hematopoietic stem cells. In this study, we demonstrate that this integrin also serves as a receptor on HUVECs for the peptide REDV from the CS5 site. The alpha 4 subunit was shown to be expressed upon HUVEC membranes by whole-cell enzyme-linked immunosorbent assay. Antifunctional antibodies directed against integrin subunits alpha 4 and beta 1 inhibited cell adhesion on REDV-grafted substrates, but not on RGD-grafted substrates. The alpha 4 subunit localized into fibrillar structures within spread cells on the REDV-grafted substrates, but not within spread cells on RGD-grafted substrates. Two proteins (144 and 120 kDa) were isolated from HUVEC extracts by REDV ligand affinity chromatography and were demonstrated by immunoprecipitation and Western blot to be the integrin subunits alpha 4 (144 kDa) and beta 1 (120 kDa); furthermore, the immunoprecipitation analyses demonstrated that the subunits formed a complex. HUVEC binding to REDV-grafted substrates was inhibited by both soluble REDV and RGD, demonstrating that adhesion was biospecific and that the REDV peptide is RGD-like. In this report we demonstrate for the first time that alpha 4 is present in the endothelial cell membrane, in contrast to previous reports by others, and that integrin alpha 4 beta 1 is the receptor for REDV-mediated adhesion to the IIICS region of region of plasma fibronectin.
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REDV enhances endothelial cell attachment by targeting the adhesion receptor α4β1 integrin.
“ELP sequences conferred the biopolymer with mechanical properties of native elastin, while REDV enhanced attachment by targeting the adhesion receptor α4 β1 integrin.”
From Liver tissue engineering using decellularized scaffolds: Current progress, challenges, and opportunities (2024) · cites this paper as [229]
The α4β1 integrin receptor is found only on the EC surface, but not on platelets.
“It is worth to mention that these receptors are found only on the ECs surface, but not on platelets [229].”
From Liver tissue engineering using decellularized scaffolds: Current progress, challenges, and opportunities (2024) · cites this paper as [229]
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References 57 · Cited by 287
- Authors
- Massia, S. P., & Hubbell, J. A.
- Affiliations
- The University of Texas at Austin (US)
- ORCID
- Hubbell, J.A.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1992-07
- Volume
- 267
- Issue
- 20
- Pages
- 14019-14026
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1565304586
- Cited by
- 287
- References
- 57
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 4 · 2023: 8 · 2022: 7 · 2021: 10 · 2020: 22 · 2019: 19 · 2018: 13 · 2017: 18 · 2016: 10 · 2015: 11 · 2014: 4 · 2013: 7 · 2012: 11
- FWCI
- 2.13
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- Funders
- National Institutes of Health (5r29hl039714-05)
- National Heart, Lung, and Blood Institute (HL 39714)
- Topics
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Physical Sciences › Materials Science › Surfaces, Coatings and Films › Polymer Surface Interaction Studies
- Keywords
- REDV peptide, endothelial cell adhesion, cell spreading, human umbilical vein endothelial cells, cell-substrate interaction
- MeSH terms
- Antibodies, Antibodies, Monoclonal, Calcium, Cell Adhesion, Cell Membrane, Cell Movement, Cells, Cultured, Endothelium, Vascular, Enzyme-Linked Immunosorbent Assay, Fibronectins, Fluorescent Antibody Technique, Humans, Oligopeptides, Peptide Fragments, Structure-Activity Relationship, Umbilical Veins, Integrins, Macromolecular Substances
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