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Author Spotlight: Development of a Method for Identifying Small Molecular Antagonists of β2 Integrin Activation
Published on: February 2, 2024
Recombinant disintegrin targets α(v) β(3) integrin and leads to mediator production
Lívia C A Ribeiro1, Lívia C Massimino1, Araceli C Durante2
1Laboratory of Clinical Immunology; Department of Clinical Analysis; College of Pharmaceutical Sciences; São Paulo State University; Araraquara, São Paulo, Brazil.
Abstract:
Integrin αvβ3 is most likely the foremost modulator of angiogenesis among all known integrins. Recombinant disintegrin DisBa-01, originally obtained from snake venom glands, binds to αvβ3, thereby significantly inhibiting adhesion and generating in vivo anti-metastatic ability. However, its function in mediator production is not clear. Here, we observed that the mediators VEGF-A, IL-8, and TGF-β are not produced by human umbilical vein endothelial cells (HUVEC cell line) or monocyte/macrophage cells (SC cell line) when cells adhered to vitronectin. However, when exposed to DisBa-01, HUVECs produced higher levels of TGF-β, and SC cells produced higher levels of VEGF-A. Nonetheless, HUVECs also showed an enhancement of apoptosis after losing adherence when exposed to disintegrin, which is a characteristic of anoikis. We propose that disintegrin DisBa-01 could be used to modulate integrin αvβ3 functions.
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