DAVID A. CARRINO, PHD
Proteoglycans are macromolecules which consist of a protein (the core protein) and covalently attached polysaccharides of a specific type known as glycosaminoglycans. Proteoglycans are found primarily outside of cells in the extracellular matrix and also at the cell surface. While these molecules were initially shown to function as structural molecules and to play a major role in conferring the physical properties to connective tissues such as cartilage and skin, more recently proteoglycans have been shown to be involved in a number of biological processes, such as cell adhesion and migration, cell proliferation, and cell signaling. Our recent research has focused on proteoglycans in human skin and how these molecules change as a function of age. While we have found several interesting age-related differences in human skin proteoglycans, one of our findings has potential implications in tissue fibrosis (i.e., scarring). We have found that the major proteoglycan in human skin is a proteoglycan known as decorin, and that adult human skin also contains a catabolic fragment of decorin. The presence of a precise C-terminus in the core protein of the catabolic fragment suggests that this catabolic fragment arises by specific cleavage of the core protein of decorin. There are a large number of extracellular matrix proteinases which exist in connective tissues and which are involved in catabolism of matrix molecules in processes such as inflammation and tissue remodeling. One of our research goals is to identify the proteinase which cleaves decorin. This work has potential implications for wound healing and scarring, because published evidence indicates that decorin has anti-scarring activity in several tissues. Elucidation of the dynamics of decorin catabolism by identifying the proteinase which cleaves decorin may allow the development of methods to reduce scarring, particularly for a group of chronic scarring diseases in human skin. If catabolism of decorin contributes to tissue fibrosis, then an understanding of this catabolic process can lead to methods for ameliorating this condition.