The extracellular matrix is a complex superstructure of macromolecules composed of glycoproteins, proteoglycans, and collagen and surrounds almost every cell in the body. The inappropriate overexpression of extracellular matrix in certain tissue has been implicated in a variety of human diseases, including glomerulonephritis and pulmonary fibrotic disease. Transforming growth factor (TGF) beta-1 has been shown to cause the accumulation of extracellular matrix by increasing the expression of matrix components, as well as by decreasing normal matrix degradation. Anti-TGF beta-1 antisera and the proteoglycan, decorin, bind TGF beta-1 and neutralize its effect on matrix overexpression thus reversing the histological manifestation of experimental and recombinant protein fragments based on the domain structure of human decorin for their ability to bind and neutralize TGF beta-1 biological activity in vitro and in vivo. These studies are intended to lead to the identification of the minimal domain of the decorin core protein required for reversal of TGF beta-1 effects and may glomerulonephritis and other matrix related diseases.
