Glycosaminoglycans and Proteoglycans: Overlooked Entities?

Abstract

By virtue of their high net negative charge, glycosaminoglycans and proteoglycans play pivotal roles in biologic processes such as cell-cell and cell-matrix interactions, sequestration of growth factors, activation of chemokines and cytokines, and permselectivity of basement membranes. The present article reviews the putative roles of glycosaminoglycans and proteoglycans in the peritoneal cavity during normal peritoneal homeostasis and chronic inflammation, the latter induced by constant exposure of the peritoneum to non-physiologic peritoneal dialysis (PD) solutions. Glycosaminoglycans have been identified in the mesothelial glycocalyx, a slippery, non-adhesive layer that protects the peritoneal membrane from abrasion and infection. Dermatan sulfate proteoglycans can neutralize the activity of transforming growth factor beta1 and can thus play an essential role in modulating peritoneal fibrosis. Heparan sulfate proteoglycans play a crucial role in the sequestration of growth factors; they also modulate selective permeability of proteins across the peritoneal cavity. Reduced expression of perlecan, a heparan sulfate proteoglycan of the basement membrane, is observed in peritoneal biopsies obtained from established PD patients, consequent to prolonged exposure to the elevated glucose concentrations in conventional PD solutions. Supplementation of PD fluids with glycosaminoglycans has been shown to be beneficial to both the structural and functional integrity of the peritoneum. Recent advances in the field of glycobiology have revealed a multitude of biologic processes that are controlled or influenced by glycosaminoglycans and proteoglycans. Altered synthesis of these macromolecules during PD has serious implications for the peritoneal transport of proteins, host defense, wound healing, inflammation, and fibrosis.