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Integrin α8 and Its Ligand Nephronectin in Health and Disease

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Integrins in Health and Disease

Part of the book series: Biology of Extracellular Matrix ((BEM,volume 13))

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Abstract

The α8 integrin is a classic arginine-glycine-aspartic acid (RGD)-binding subunit that partners exclusively with the β1 subunit. α8 is expressed by mesenchymal cells, particularly vascular and visceral smooth muscle cells (SMCs) and highly contractile fibroblasts, that are associated with basal laminae. While α8 recognizes typical RGD-containing ligands such as fibronectin, it shows an exceptional affinity for nephronectin (NPNT), a basement membrane protein that has both an RGD and a synergistic binding site for α8. NPNT was identified as the key signaling ligand for α8 in kidney morphogenesis. Although both α8 and NPNT contribute to the development of other organs, such as hair follicles, lack of phenotypic differences in the global KOs as compared to wild-type are often explainable by compensatory mechanisms. Studies using either cells or mice deficient in α8 indicate that, in general, this integrin subunit is required for the maintenance of SMC differentiation and is protective against the sequelae of injury, especially in the kidney. Although less is known about NPNT in tissue injury, its expression also appears to correlate with repair. Finally, dysregulated expression of NPNT and α8 has been recently described in several cancers, suggesting that these proteins may be novel targets for future therapeutic intervention.

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Authors and Affiliations

  1. Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA

    Carole L. Wilson & Lynn M. Schnapp

  2. Division of Pulmonary, Critical Care, and Sleep Medicine, University of Washington, Seattle, WA, USA

    Chi F. Hung

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  1. Carole L. Wilson
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  2. Chi F. Hung
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  3. Lynn M. Schnapp
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Correspondence to Lynn M. Schnapp .

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  1. Department of Biomedicine and Centre for Cancer Biomarkers, Norwegian Centre of Excellence, University of Bergen, Bergen, Norway

    Donald Gullberg

  2. University of Münster, Münster, Germany

    Johannes A. Eble

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Wilson, C.L., Hung, C.F., Schnapp, L.M. (2023). Integrin α8 and Its Ligand Nephronectin in Health and Disease. In: Gullberg, D., Eble, J.A. (eds) Integrins in Health and Disease. Biology of Extracellular Matrix, vol 13. Springer, Cham. https://doi.org/10.1007/978-3-031-23781-2_5

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