TSG-6: A multifunctional protein with anti-inflammatory and tissue-protective properties

Matrix Biol. 2019 May:78-79:60-83. doi: 10.1016/j.matbio.2018.01.011. Epub 2018 Jan 31.

Abstract

Tumor necrosis factor- (TNF) stimulated gene-6 (TSG-6) is an inflammation-associated secreted protein that has been implicated as having important and diverse tissue protective and anti-inflammatory properties, e.g. mediating many of the immunomodulatory and beneficial activities of mesenchymal stem/stromal cells. TSG-6 is constitutively expressed in some tissues, which are either highly metabolically active or subject to challenges from the environment, perhaps providing protection in these contexts. The diversity of its functions are dependent on the binding of TSG-6 to numerous ligands, including matrix molecules such as glycosaminoglycans, as well as immune regulators and growth factors that themselves interact with these linear polysaccharides. It is becoming apparent that TSG-6 can directly affect matrix structure and modulate the way extracellular signalling molecules interact with matrix. In this review, we focus mainly on the literature for TSG-6 over the last 10 years, summarizing its expression, structure, ligand-binding properties, biological functions and highlighting TSG-6's potential as a therapeutic for a broad range of disease indications.

Keywords: Chemokines; Hyaluronan; Inflammation; MSCs; Matrix reorganization; TSG-6.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Adhesion Molecules / chemistry*
  • Cell Adhesion Molecules / metabolism*
  • Extracellular Matrix / metabolism
  • Glycosaminoglycans / metabolism
  • Humans
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Mesenchymal Stem Cells / immunology*
  • Models, Molecular
  • Protein Binding
  • Protein Conformation
  • Signal Transduction

Substances

  • Cell Adhesion Molecules
  • Glycosaminoglycans
  • Intercellular Signaling Peptides and Proteins
  • TNFAIP6 protein, human