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Eosinophil Interactions with Extracellular Matrix Proteins
Published in Bruce S. Bochner, Adhesion Molecules in Allergic Disease, 2020
Garry M. Walsh, Andrew J. Wardlaw
Other ECM proteins include the collagens, which are a highly specialized glycoprotein family with a least 16 distinct members that are thought to be encoded by at least 30 genes (9). Collagens are very widespread, being found in the stroma, basement membranes, cartilage, tumors, skin, tendons, and, in the case of asthma, the thickened layer of connective tissue found below the epithelium (primarily collagen type IV). Vitronectin has been identified in both the ECM and plasma, the latter being found as either a single or two-chain form held together by disulfide bridges. The form found in tissues is not yet known. Vitronectin is encoded by a single gene and has a variety of functions, being involved in phagocytosis, tissue repair, and immune function. Cellular attachment to vitronectin is mediated by αvβ3, αIIbβ3, and αvβ5 via an RGD sequence (33).
Dermal Fibroblast Function
Published in Brian J. Nickoloff, Dermal Immune System, 2019
The composition of the surface on which fibroblasts are grown determines the degree to which they adhere to that surface. Fibroblasts adhere, spread, and develop focal adhesions better on surfaces coated with extracellular matrix proteins such as fibronectin or vitronectin, and adhere poorly and do not develop focal adhesions when they are plated on glass in serum-free medium or medium supplemented only with bovine serum albumin.75 Serum-spreading factor (vitronectin) is probably the major extracellular component of focal adhesions when cells are grown in serum-containing medium.73,76 Vitronectin, like fibronectin, has a heparin-binding domain and an Arg-Gly-Asp (RGD) sequence that is also common to other matrix proteins that interact with cells.73,77 Both the heparin-binding domain and the RGD sequence are necessary for formation of focal adhesions by cells.73,78
Coagulation and the coagulation cascade
Published in John Edward Boland, David W. M. Muller, Interventional Cardiology and Cardiac Catheterisation, 2019
John Edward Boland, David E. Connor
Platelets also have glycoproteins on their surface that act as receptors for several adhesive proteins that enable platelets to bind selectively to vessel walls and each other. There are nine major platelet glycoproteins, numbered I to IX. Glycoprotein Ia (GP Ia) binds platelets directly to collagen, while glycoproteins Ib, IIb, and IIIa (GP Ib, GP IIb, GP IIIa) bind to Von Willebrand factor (VWF, a component of factor VIII plasma protein), which itself has receptors that bind to myofibrils in smooth muscle cells. Glycoproteins fibronectin and vitronectin are also involved in platelet binding.
Understanding collagen interactions and their targeted regulation by novel drugs
Published in Expert Opinion on Drug Discovery, 2021
Marialucia Gallorini, Simone Carradori
Vitronectin (VN) is a multifunctional glycoprotein which binds to different biological ligands and, by binding to different types of integrins, mostly via the RGD sequence, plays a key role in tissue remodeling by controlling cell adhesion. In addition to that, VN owns two domains for collagen-binding and interacts with collagens I, II, III, IV, V and VI. As for fibronectin (FN), its interactions with collagen are crucial during the genesis of fibrils. Fibronectin has also been discovered as a target protein for the diagnosis of high-risk micro-metastasis of breast cancer. A successful approach to prevent metastatic invasion could be the selective delivery of therapeutic drugs to highly fibronectin-expressing metastatic tumor sites [93]. Finally, the crosstalk between collagens and non-collagenous bone proteins, such as bone sialoprotein II (BSPII) and osteonectin (SPARC, secreted protein acidic and rich in cysteine), is involved in tissue remodeling and cancer-related metastases. The SPARC protein has furthermore been identified as a potential therapeutic target to prevent breast cancer bone metastasis [94].
Anti-integrin therapy for retinovascular diseases
Published in Expert Opinion on Investigational Drugs, 2020
Ashay D. Bhatwadekar, Viral Kansara, Qianyi Luo, Thomas Ciulla
SF-0166 (SciFluor Life Science, MA, USA) is a small molecule inhibitor of integrin αvβ3. Due to its optimized physicochemical properties, SF-0166 can distribute to the posterior segment of the eye after topical administration, and the drug concentration was maintained for more than 12 hours [64]. In in vitro studies, SF-0166 was shown to inhibit cell adhesion to vitronectin across a variety of cell lines of rat, rabbit, dog origin, and shown to inhibit integrin-ligand interactions for the human dermal microvascular endothelial cells. In addition to αvβ3, SF-0166 also inhibits integrins αvβ6, and αvβ8 at nanomolar concentrations; however, it does not inhibit binding to αvβ5 or fibronectin via α5β1 integrins [64]. SF-0166 was found to inhibit neovascularization in the oxygen-induced retinopathy mouse model after topical administration. In the laser-induced CNV animal model, SF-0166 decreased lesion area; this decrease was comparable to bevacizumab. In the rabbit model of VEGF-induced vascular leakage model, topically delivered SF-0166 exhibited a dose-dependent reduction in vascular leakage [64].
How useful are ferric chloride models of arterial thrombosis?
Published in Platelets, 2020
Steven P. Grover, Nigel Mackman
Thiol isomerases, such as protein disulfide isomerase (PDI), ERp57 and ERp72, are a family of enzymes that catalyze the rearrangement of disulfide bonds. Recent studies have shown a role of these enzymes in arterial thrombosis. In the carotid artery, mesenteric arteriole ferric chloride and cremaster arteriole laser injury models deletion of PDI in platelets significantly impaired thrombus formation [38,39]. Similarly, deletion of ERp57 and ERp72 reduced arterial thrombus formation in the ferric chloride and laser injury models [40–43]. Interestingly, the presence of a phenotype in mice deficient for either PDI, ERp57 or ERp72 suggests that each of these thiol isomerase enzymes independently contribute to thrombus formation. Recent work has identified vitronectin as an important substrate for PDI mediated arterial thrombus formation [33].