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

• Published in: Matrix biology Vol. 78-79; pp. 60 - 83
• Main Authors: Day, Anthony J., Milner, Caroline M.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.05.2019; Elsevier Science Ltd
• Subjects: Animals; Antiinflammatory agents; Cell Adhesion Molecules - chemistry; Cell Adhesion Molecules - metabolism; Chemokines; Extracellular Matrix - metabolism; Glycosaminoglycans; Glycosaminoglycans - metabolism; Growth factors; Humans; Hyaluronan; Immunomodulation; Inflammation; Intercellular Signaling Peptides and Proteins - metabolism; Matrix reorganization; Mesenchymal Stem Cells - immunology; Mesenchyme; Models, Molecular; MSCs; Polysaccharides; Protein Binding; Protein Conformation; Signal Transduction; Stromal cells; TSG-6; Tumor necrosis factor; Tumor necrosis factor-TNF; IαI; T1D; FN; PαI; AHR; HS; HC•HA; TNF; LPS; DS; Hyaluronan; MSCs; OA; ECs; DCs; COC; TSG-6; HC•TSG-6; IL; BMP; Inflammation; AM; GAG; BAL; GFAP; RA; CS; TSP; PG; TK; Matrix reorganization; TGFβ; HA; PTX3; HC; Chemokines
• ISSN: 0945-053X; 1569-1802; 1569-1802
• DOI: 10.1016/j.matbio.2018.01.011

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. •TSG-6 is a multifunctional protein that regulates matrix organization and structure•TSG-6 modulates interactions of chemokines with sulfated glycosaminoglycans on the cell surface•TSG-6 is implicated in mediating anti-inflammatory and tissue-protective functions of MSCs•TSG-6 treatment has efficacious effects in a broad range of disease models•The expression, structure and ligand-binding properties of TSG-6 underpin its diverse biology and therapeutic potential