Glycosaminoglycan-protein and protein-protein interactions in inflammatory processes

Lead Research Organisation: University of Manchester
Department Name: Life Sciences

Abstract

Important results from research will be disseminated to the public and special interest groups through press releases and by contributions to lay publications (e.g., Arthritis Today).

Technical Summary

Glycosaminoglycans (GAGs) are polysaccharides with a central role in the regulation of protein and cell function in particular tissue microenvironments. For example, the interaction of hyaluronan - a high molecular weight GAG - with specific hyaluronan-binding proteins (hyaladherins) is critical for the formation and stability of extracellular matrix (e.g. in cartilage) and is also important in immune cell trafficking. One of the main aims of my research is to determine the structural basis and molecular regulation of hyaluronan-protein interactions. This work is focused primarily on TSG-6 - a multifunctional protein that is essential for ovulation (an inflammation-like process) and is also produced during inflammatory disease (e.g. arthritis) where it has anti-inflammatory properties and may play a role in tissue repair. Other hyaladherins under study are CD44 (a ubiquitous cell surface receptor for hyaluronan), which is involved in matrix assembly and leukocyte migration, and the extracellular matrix components aggrecan, versican and link protein that are crucial for matrix structure. In addition to hyaluronan, TSG-6 binds to sulphated GAGs (i.e. heparin, heparan sulphate, chondroitin-4-sulphate and dermatan sulphate) as well as a growing list of proteins (e.g. aggrecan, inter- -inhibitor, PTX3, TSP1) where these interactions have differential effects on its functional activities. This makes TSG-6 an ideal model system to investigate microenvironment control in inflammatory processes both at a structural and functional level.

Publications

10 25 50
 
Description Collaborationn with Seikagaku 
Organisation Seikagaku Corporation
Country Japan 
Sector Private 
PI Contribution We supplied protein and expertise to allow studies on the potential of our biological drug (Link_TSG6) for the treatment of osteoarthritis to be carried out by Seikagaku Corporation, Japan.
Collaborator Contribution Seikagaku Corporation (Japan) assessed the potential of our protein-based biological for the treatment of osteoarthritis. New discussions are ongoing about the use of Link_TSG6 for treating ocular symptoms associated with Sjogren's syndrome.
Impact No outputs as yet.
Start Year 2016