Proteoglycans in Cell Regulation

Proteoglycans are a diverse group of proteins carrying one or more glycosaminoglycan side chains linked to the protein as O-glycosides. Our appreciation of these structures has matured from a curiosity about unusual structural glycoproteins, to confer upon them a central role in cell biology. The major classes of glycosaminoglycans are heparan sulfate and heparin, chondroitin and dermatan sulfates, keratan sulfate and hyaluronic acid. The latter is unique in that it does not contain sulfate residues, and appears to be synthesized, at least sometimes, free of a carrier protein. There is now a wealth of information on the ability of these structures to influence the growth and development of cells and tissues. Many direct and specific effects of proteoglycans will undoubtedly be found, and there are likely to be indirect effects of the glycosaminoglycans relating to their polyelectrolyte nature. Convincing arguments that biological activity resides in certain proteoglycan core proteins are also appearing. The following discussion concerns the role of proteoglycans in the regulation and action of autocrine and polypeptide growth factors, direct mitogenic and antimitogenic actions of glycosaminoglycans, the role of these structures in regulating gene expression, and the biological activities of proteoglycan core proteins. The probable role of proteoglycans in normal glomerular cell function, and in progressive renal disease, will be presented as a harbinger of the significant role we can expect them to play in diagnosis and therapy in the near future.