Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
9.4
4.8
Journals
Biomolecules
Special Issues
New Insights into Integrins
share announcement

New Insights into Integrins

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Biological Factors".

Deadline for manuscript submissions: 30 November 2025 | Viewed by 8159

Special Issue Editor

Prof. Dr. Yoshikazu Takada

E-Mail Website
Guest Editor
Department of Dermatology, School of Medicine, University of California–Davis, 4645 Second Ave., Research III Suite 3300, Sacramento, CA 95817, USA
Interests: integrin-growth factor crosstalk; regulation of integrin activation; identification of new integrin ligands
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Integrins were originally identified as a family of receptors for extracellular molecules (e.g., fibronectin) and cell surface molecules (e.g., ICAM-1) in the 1980s. Since, it has been discovered that integrins also interact with soluble ligands such as growth factors (e.g., FGF-1, IGF-1), and almost a decade ago, that several growth factors bind to integrins and cognate receptors simultaneously and generate an integrin–growth factor–cognate receptor ternary complex (ternary complex model). Moreover, growth factor mutants defective in integrin binding are defective in signaling and act as antagonists. It has been recently shown that the a6b1–FGF2–FGFR ternary complex plays a critical role in stem cell maintenance. Additionally, we identified an allosteric site of integrins (site 2) which is distinct from the classical RGD-binding site. Several integrin ligands (e.g., inflammatory chemokines and inflammatory proteins such as secreted PLA2-IIA) bind and induce integrin activation in an allosteric manner. Site 2 was shown to be a binding site for an inflammatory lipid mediator (25-hydroxycholesterol) and is involved in inflammatory signaling in innate immunity. The integrin–growth factor interaction and allosteric activation through site 2 should pave the path to new therapeutic targets. Thus, this Special Issue is designed to facilitate the progress of newly opened fields of integrin study.

Prof. Dr. Yoshikazu Takada
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomolecules is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • integrins
  • growth factors
  • ligands

Benefits of Publishing in a Special Issue

  • Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
  • Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
  • Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
  • External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
  • e-Book format: Special Issues with more than 10 articles can be published as dedicated e-books, ensuring wide and rapid dissemination.

Further information on MDPI's Special Issue policies can be found here.

Published Papers (6 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

Jump to: Review

22 pages, 3646 KiB  
Article
Determining Ligand Binding and Specificity Within the β2-Integrin Family with a Novel Assay Platform
by Carla Johanna Sommer-Plüss, Céline Leiggener, Elira Nikci, Riccardo Vincenzo Mancuso, Said Rabbani, Christina Lamers and Daniel Ricklin
Biomolecules 2025, 15(2), 238; https://doi.org/10.3390/biom15020238 - 7 Feb 2025
Viewed by 856
Abstract
The family of the β2-integrin receptors is critically involved in host defense and homeostasis, by mediating immune cell adhesion, migration, and phagocytosis. Due to their key roles in immune surveillance and inflammation, their modulation has been recognized as an attractive drug [...] Read more.
The family of the β2-integrin receptors is critically involved in host defense and homeostasis, by mediating immune cell adhesion, migration, and phagocytosis. Due to their key roles in immune surveillance and inflammation, their modulation has been recognized as an attractive drug target. However, the development of therapeutics has been limited, partly due to the high promiscuity of endogenous ligands, their functional responses, and gaps in our understanding of their disease-related molecular mechanisms. The delineation of the molecular role of β2 integrins and their ligands has been hampered by a shortage of validated assay systems. To facilitate molecular and functional studies on the β2-integrin family, and to enable screening of modulators, this study provides a uniform and validated assay platform. For this purpose, the major ligand-binding domains (αI) of all four β2 integrins were recombinantly expressed in both low- and high-affinity states. By optimizing the expression parameters and selecting appropriate purification tags, all αI-domain variants could be produced with high yield and purity. Direct binding studies using surface plasmon resonance (SPR) confirmed the expected activity and selectivity profiles of the recombinant αI domains towards their reported ligands, validating our approach. In addition, the SPR studies provided additional insights into ligand binding, especially for the scarcely described family member CD11d. Alongside characterizing endogenous ligands, the platform can be employed to test pharmacologically active compounds, such as the reported β2-integrin antagonist simvastatin. In addition, we established a bead-based adhesion assay using the recombinant αI domains, and a cell-based adhesion assay underlining most findings generated with the isolated αI domains. Interestingly, the binding of ligands to the recombinant αDI is not dependent on divalent cation, in contrast to the full integrin CD11d/CD18, suggesting a binding mode distinct of the metal ion-dependent adhesion site (MIDAS). The setup highlights the applicability of recombinant αI domains for first screenings and direct or competitive interaction studies, while the full integrin is needed to validate those findings. Full article
(This article belongs to the Special Issue New Insights into Integrins)
►▼ Show Figures

Figure 1

15 pages, 4585 KiB  
Article
Effect of Integrin Blockade on Experimental Spondyloarthritis
by Enoch Yau, Melissa Lim, Zoya Qaiyum, Shaghayegh Foroozan Boroojeni, Michael Tang, Addison Pacheco, Fataneh Tavasolian and Robert D. Inman
Biomolecules 2024, 14(11), 1386; https://doi.org/10.3390/biom14111386 - 31 Oct 2024
Viewed by 1137
Abstract
Spondyloarthritis (SpA) describes a group of diseases characterized by chronic inflammation in the spine and peripheral joints. While pathogenesis is still unclear, proinflammatory gut-derived immune cells have been identified in the joints of SpA patients. We previously identified an enriched population of integrin-expressing [...] Read more.
Spondyloarthritis (SpA) describes a group of diseases characterized by chronic inflammation in the spine and peripheral joints. While pathogenesis is still unclear, proinflammatory gut-derived immune cells have been identified in the joints of SpA patients. We previously identified an enriched population of integrin-expressing cells in the joints of SpA patients. Entry of gut-derived cells into joints may be mediated by these integrins. In the current study, we used the SKG murine model of SpA to study the impact of integrin blockade. Mice were injected with antibodies against the integrin α4β7 or the β7 monomer twice a week. Treatment with antibodies against α4β7 reduced disease severity in curdlan-injected SKG mice, with disease scores being comparable between treatment initiation times. Targeting the β7 monomer led to reduced arthritis severity compared to targeting the α4β7 dimer. Treatment with antibodies against α4β7 or β7 decreased expression of these integrins in CD4+ T cells, with the frequency of αE+β7+ T cells in the spleen and lymph nodes correlating with disease severity. In summary, we showed that integrin blockade showed potential for ameliorating disease in a murine model of SpA, lending support for further studies testing integrin blockade in SpA. Full article
(This article belongs to the Special Issue New Insights into Integrins)
►▼ Show Figures

Figure 1

13 pages, 2343 KiB  
Article
Collagen I Increases Palmitate-Induced Lipotoxicity in HepG2 Cells via Integrin-Mediated Death
by Tumisang Edward Maseko, Eva Peterová, Moustafa Elkalaf, Darja Koutová, Jan Melek, Pavla Staňková, Veronika Špalková, Reem Matar, Halka Lotková, Zuzana Červinková and Otto Kučera
Biomolecules 2024, 14(9), 1179; https://doi.org/10.3390/biom14091179 - 20 Sep 2024
Viewed by 1572
Abstract
Various strategies have been employed to improve the reliability of 2D, 3D, and co-culture in vitro models of nonalcoholic fatty liver disease, including using extracellular matrix proteins such as collagen I to promote cell adhesion. While studies have demonstrated the significant benefits of [...] Read more.
Various strategies have been employed to improve the reliability of 2D, 3D, and co-culture in vitro models of nonalcoholic fatty liver disease, including using extracellular matrix proteins such as collagen I to promote cell adhesion. While studies have demonstrated the significant benefits of culturing cells on collagen I, its effects on the HepG2 cell line after exposure to palmitate (PA) have not been investigated. Therefore, this study aimed to assess the effects of PA-induced lipotoxicity in HepG2 cultured in the absence or presence of collagen I. HepG2 cultured in the absence or presence of collagen I was exposed to PA, followed by analyses that assessed cell proliferation, viability, adhesion, cell death, mitochondrial respiration, reactive oxygen species production, gene and protein expression, and triacylglycerol accumulation. Culturing HepG2 on collagen I was associated with increased cell proliferation, adhesion, and expression of integrin receptors, and improved cellular spreading compared to culturing them in the absence of collagen I. However, PA-induced lipotoxicity was greater in collagen I-cultured HepG2 than in those cultured in the absence of collagen I and was associated with increased α2β1 receptors. In summary, the present study demonstrated for the first time that collagen I-cultured HepG2 exhibited exacerbated cell death following exposure to PA through integrin-mediated death. The findings from this study may serve as a caution to those using 2D models or 3D scaffold-based models of HepG2 in the presence of collagen I. Full article
(This article belongs to the Special Issue New Insights into Integrins)
►▼ Show Figures

Figure 1

18 pages, 3609 KiB  
Article
FGF1 Suppresses Allosteric Activation of β3 Integrins by FGF2: A Potential Mechanism of Anti-Inflammatory and Anti-Thrombotic Action of FGF1
by Yoko K. Takada, Xuesong Wu, David Wei, Samuel Hwang and Yoshikazu Takada
Biomolecules 2024, 14(8), 888; https://doi.org/10.3390/biom14080888 - 23 Jul 2024
Cited by 1 | Viewed by 1209
Abstract
Several inflammatory cytokines bind to the allosteric site (site 2) and allosterically activate integrins. Site 2 is also a binding site for 25-hydroxycholesterol, an inflammatory lipid mediator, and is involved in inflammatory signaling (e.g., TNF and IL-6 secretion) in addition to integrin activation. [...] Read more.
Several inflammatory cytokines bind to the allosteric site (site 2) and allosterically activate integrins. Site 2 is also a binding site for 25-hydroxycholesterol, an inflammatory lipid mediator, and is involved in inflammatory signaling (e.g., TNF and IL-6 secretion) in addition to integrin activation. FGF2 is pro-inflammatory and pro-thrombotic, and FGF1, homologous to FGF2, has anti-inflammatory and anti-thrombotic actions, but the mechanism of these actions is unknown. We hypothesized that FGF2 and FGF1 bind to site 2 of integrins and regulate inflammatory signaling. Here, we describe that FGF2 is bound to site 2 and allosterically activated β3 integrins, suggesting that the pro-inflammatory action of FGF2 is mediated by binding to site 2. In contrast, FGF1 bound to site 2 but did not activate these integrins and instead suppressed integrin activation induced by FGF2, indicating that FGF1 acts as an antagonist of site 2 and that the anti-inflammatory action of FGF1 is mediated by blocking site 2. A non-mitogenic FGF1 mutant (R50E), which is defective in binding to site 1 of αvβ3, suppressed β3 integrin activation by FGF2 as effectively as WT FGF1. Full article
(This article belongs to the Special Issue New Insights into Integrins)
►▼ Show Figures

Figure 1

Review

Jump to: Research

27 pages, 883 KiB  
Review
Integrins in Cardiovascular Health and Disease: Molecular Mechanisms and Therapeutic Opportunities
by Karolina Ławkowska, Klaudia Bonowicz, Dominika Jerka, Yidong Bai and Maciej Gagat
Biomolecules 2025, 15(2), 233; https://doi.org/10.3390/biom15020233 - 6 Feb 2025
Viewed by 1224
Abstract
Cardiovascular diseases, including atherosclerosis, hypertension, and heart failure, remain the leading cause of global mortality, with endothelial dysfunction and vascular remodeling as critical contributors. Integrins, as transmembrane adhesion proteins, are central regulators of cell adhesion, migration, and signaling, playing a pivotal role in [...] Read more.
Cardiovascular diseases, including atherosclerosis, hypertension, and heart failure, remain the leading cause of global mortality, with endothelial dysfunction and vascular remodeling as critical contributors. Integrins, as transmembrane adhesion proteins, are central regulators of cell adhesion, migration, and signaling, playing a pivotal role in maintaining vascular homeostasis and mediating pathological processes such as inflammation, angiogenesis, and extracellular matrix remodeling. This article comprehensively examines the role of integrins in the pathogenesis of cardiovascular diseases, focusing on their dysfunction in endothelial cells and interactions with inflammatory mediators, such as TNF-α. Molecular mechanisms of integrin action are discussed, including their involvement in mechanotransduction, leukocyte adhesion, and signaling pathways that regulate vascular integrity. The review also highlights experimental findings, such as the use of specific integrin-targeting plasmids and immunofluorescence to elucidate integrin functions under inflammatory conditions. Additionally, potential therapeutic strategies are explored, including the development of integrin inhibitors, monoclonal antibodies, and their application in regenerative medicine. These approaches aim not only to mitigate pathological vascular remodeling but also to promote tissue repair and angiogenesis. By bridging insights from molecular studies with their translational potential, this work underscores the promise of integrin-based therapies in advancing the management and treatment of cardiovascular diseases. Full article
(This article belongs to the Special Issue New Insights into Integrins)
►▼ Show Figures

Figure 1

24 pages, 1973 KiB  
Review
Integrin and Its Associated Proteins as a Mediator for Mechano-Signal Transduction
by Kazuo Katoh
Biomolecules 2025, 15(2), 166; https://doi.org/10.3390/biom15020166 - 23 Jan 2025
Viewed by 1509
Abstract
Mechano-signal transduction is a process in which cells perceive extracellular mechanical signals, convert them into intracellular biochemical signals, and produce a response. Integrins are cell surface receptors that sense the extracellular mechanical cues and bind to the extracellular matrix (ECM). This binding induces [...] Read more.
Mechano-signal transduction is a process in which cells perceive extracellular mechanical signals, convert them into intracellular biochemical signals, and produce a response. Integrins are cell surface receptors that sense the extracellular mechanical cues and bind to the extracellular matrix (ECM). This binding induces integrin clustering and activation. Cytoplasmic tails of activated integrins interact and induce cytoskeleton tensions via several adaptor proteins. Integrins monitor extracellular stiffness via cytoskeleton tensions and modulate ECM stiffness via downstream signaling pathways regulating the expression of genes of ECM components. Integrin-mediated mechano-transduction is very crucial for the cell as it regulates the cell physiology both in normal and diseased conditions according to extracellular mechanical cues. It regulates cell proliferation, survival, and migration. Abnormal mechanical cues such as extreme and prolonged mechanical stress result in pathological conditions including fibrosis, cancers, skin, and autoimmune disorders. This paper aims to explore the role of integrins and their associated proteins in mechano-signal transduction. It highlights the integrins and their associated proteins as targets for therapy development. Furthermore, it also presents the challenges to the targeted drug development, which can be drug resistance and cytotoxicity. It is concluded in this paper that research on integrin-mediated mechano-signal transduction and its relationship with cell physiology and pathologies will be an important step towards the development of effective therapies. Full article
(This article belongs to the Special Issue New Insights into Integrins)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-6
Back to TopTop