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Versican and the regulation of cell phenotype in disease
Authors:Thomas N. Wight  Michael G. Kinsella  Stephen P. Evanko  Susan Potter-Perigo  Mervyn J. Merrilees
Affiliation:1. Matrix Biology Program, Benaroya Research Institute at Virginia Mason, Seattle, WA, USA;2. Department of Anatomy with Radiology, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
Abstract:

Background

Versican is an extracellular matrix (ECM) proteoglycan that is present in the pericellular environment of most tissues and increases in many different diseases. Versican interacts with cells to influence the ability of cells to proliferate, migrate, adhere and assemble an ECM.

Scope of review

The structure of the versican molecule is briefly reviewed and studies highlighting those factors that promote versican synthesis and degradation and their impact on cell phenotype in disease are discussed. Particular attention is given to vascular disease, but other diseases where versican is important are covered as well, most notably different forms of cancers. Attention is given to mechanisms(s) by which versican influences cell behaviors through either direct or indirect processes. Versican produced by either stromal cells or myeloid cells can have a major impact influencing immunity and inflammation. Finally, studies controlling versican accumulation that either delay or inhibit the progression of disease will be highlighted.

Major conclusions

Versican is one component of the ECM that can influence the ability of cells to proliferate, migrate, adhere, and remodel the ECM. Targeting versican as a way to control cell phenotype offers a novel approach in the treatment of disease.

Significance

ECM molecules such as versican contribute to the structural integrity of tissues and interact with cells through direct and indirect means to regulate, in part, cellular events that form the basis of disease. This article is part of a Special Issue entitled Matrix-mediated cell behaviour and properties.
Keywords:ECM, Extracellular matrix   HA, hyaluronan   GAG, glycosaminoglycan   CS, chondroitin sulfate   ASMCs, arterial smooth muscle cells   PDGF, platelet-derived growth factor   KO, knockout   miRNA, microRNA   UTR, untranslated region   CNS, central nervous system   MMPs, matrix metalloproteinases   PSGL-1, P-selectin glycoprotein-1   ADAMTS, A Disintegrin And Metalloproteinase with Thrombospondin Motifs   SNPs, single nucleotide polymorphisms   EGF, epidermal growth factor   TLR2, toll-like receptor 2   FAK, focal adhesion kinase   IαI, inter-alpha-trypsin inhibitor   ER, endoplasmic reticulum
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