Tumor Necrosis Factor-stimulated Gene-6 (TSG-6) Is Constitutively Expressed in Adult Central Nervous System (CNS) and Associated with Astrocyte-mediated Glial Scar Formation following Spinal Cord Injury.

Abstract

Tumor necrosis factor (TNF)-stimulated gene-6 (TSG-6) binds to hyaluronan and can reorganize/stabilize its structure, also enhancing the binding of this glycosaminoglycan to its cell surface receptor, CD44. TSG-6 is rapidly up-regulated in response to inflammatory cytokines protecting tissues from the damaging effects of inflammation. Despite TSG-6 treatment having been shown to improve outcomes in an experimental model of traumatic brain injury, TSG-6 expression has not been extensively studied in the central nervous system (CNS). We hereby analyzed the expression profile of TSG-6 in the developing CNS and following injury. We show that TSG-6 is expressed in the rat CNS by GFAP(+) and CD44(+) astrocytes, solely in the mature brain and spinal cord, and is not present during the development of the CNS. TSG-6(-/-) mice present a reduced number of GFAP(+) astrocytes when compared with the littermate TSG-6(+/-) mice. TSG-6 expression is drastically up-regulated after injury, and the TSG-6 protein is present within the glial scar, potentially coordinating and stabilizing the formation of this hyaluronan-rich matrix. This study shows that TSG-6 is expressed in the CNS, suggesting a role for TSG-6 in astrocyte activation and tissue repair. We hypothesize that within this context TSG-6 could participate in the formation of the glial scar and confer anti-inflammatory properties. Further studies are required to elucidate the therapeutic potential of targeting TSG-6 after CNS injury to promote its protective effects while reducing the inhibitory properties of the glial scar in axon regeneration.

• Authors: Vivien J Coulson-Thomas, Mark E Lauer, Sara Soleman, Chao Zhao, Vincent C Hascall, Anthony J Day, James W Fawcett
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 291 Issue 38 Pg. 19939-52 (09 16 2016) ISSN: 1083-351X [Electronic] United States
• PMID: 27435674 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Chemical References

• Cell Adhesion Molecules
• Nerve Tissue Proteins
• Tnfaip6 protein, mouse

Topics

• Animals
• Astrocytes (metabolism, pathology)
• Axons (metabolism, pathology)
• Brain (metabolism, pathology)
• Cell Adhesion Molecules (biosynthesis, genetics)
• Cicatrix (genetics, metabolism, pathology)
• Gene Expression Regulation
• Mice
• Mice, Knockout
• Nerve Tissue Proteins (biosynthesis)
• Rats
• Rats, Sprague-Dawley
• Spinal Cord (metabolism, pathology)
• Spinal Cord Injuries (genetics, metabolism, pathology)