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Versican and the control of inflammation.

Abstract
Versican is an extracellular matrix (ECM) proteoglycan that interacts with cells by binding to non-integrin and integrin receptors and to other ECM components that associate with the cell surface. Recent studies have shown also that versican interacts with myeloid and lymphoid cells promoting their adhesion and production of inflammatory cytokines. Versican is produced by stromal cells, as well as leukocytes, and is markedly increased in inflammation. Inflammatory agonists, such as double-stranded RNA mimetics (e.g., poly I:C), stimulate stromal cells, smooth muscle cells and fibroblasts, to produce fibrillar ECMs enriched in versican and hyaluronan (HA) that interact with leukocytes promoting their adhesion. Interference with the incorporation of versican into this ECM blocks monocyte adhesion and dampens the inflammatory response. Tumor cells also express elevated levels of versican which interact with myeloid cells to promote an inflammatory response, through stimulating cytokine release, and metastasis. In addition, myeloid cells, such as macrophages in tumors, synthesize versican which affects tumor cell phenotypes, inflammation, and subsequent metastasis. Versican, by binding to hyaluronan, influences T lymphocyte phenotypes and in part controls the ability of these cells to synthesize and secrete cytokines that influence the immune response. Collectively, these studies indicate that versican as an ECM molecule plays a central role in inflammation and as a result it is emerging as a potential target promising wide therapeutic benefits.
AuthorsThomas N Wight, Inkyung Kang, Mervyn J Merrilees
JournalMatrix biology : journal of the International Society for Matrix Biology (Matrix Biol) Vol. 35 Pg. 152-61 (Apr 2014) ISSN: 1569-1802 [Electronic] Netherlands
PMID24513039 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review)
CopyrightCopyright © 2014 International Society of Matrix Biology. Published by Elsevier B.V. All rights reserved.
Chemical References
  • Protein Isoforms
  • Versicans
Topics
  • Animals
  • Cell Adhesion (physiology)
  • Extracellular Matrix (metabolism)
  • Genetic Vectors
  • Humans
  • Inflammation (metabolism, prevention & control)
  • Lymphocyte Activation (immunology)
  • Lymphocytes (metabolism)
  • Mice
  • Models, Biological
  • Molecular Structure
  • Myeloid Cells (metabolism)
  • Protein Isoforms (genetics, metabolism)
  • Retroviridae
  • T-Lymphocytes (physiology)
  • Transduction, Genetic
  • Versicans (chemistry, genetics, metabolism)

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