CD44 IN GLOMERULONEPHRITIS - EXPRESSION IN HUMAN RENAL BIOPSIES, THE THY-1.1 MODEL, AND BY CULTURED MESANGIAL CELLS

CD44 is a transmembrane proteoglycan that serves as a cell adhesion re ceptor and is involved in cell-cell and cell-matrix interactions, both key events in the pathogenesis of clinical and experimental glomerulo nephritis. In addition, recent evidence suggests that the binding of c ytokines to proteoglycans could regulate cytokine function. We have, t herefore, studied the expression of CD44 by mesangial cells in culture and in experimental (Thy 1.1 model) and human glomerulonephritis. Mes angial expression of CD44 detected by immunohistochemistry was markedl y increased four days after induction of the Thy 1.1 model? coinciding with the peak of mesangial cell proliferation and macrophage infiltra tion. Analysis of 92 human renal biopsies by immunohistochemistry show ed that CD44 expression by infiltrating cells within the glomerulus, i n focal interstitial infiltrates and within the interstitium (intersti tial fibroblasts, and extracellular matrix), was significantly increas ed in biopsies with a greater degree of histological damage. There was , however, no increase in mesangial staining in diseased kidneys as co mpared with control sections. In contrast, cultured human mesangial ce lls expressed CD44 strongly when assayed by immunohistochemistry, immu noprecipitation and Northern blotting. CD44, therefore, is an example of a protein strongly expressed by mesangial cells in vitro and weakly or not at all in vivo, but which is up-regulated in a disease model. In human disease; however, little expression was detected within the g lomerular mesangium, which map be related to the greater proliferation and more profound disruption of mesangial architecture seen in the Th y 1.1 model. CD44 expression by infiltrating cells and by components o f the interstitium could, however, play an important role in the patho genesis of chronic progressive renal disease in humans.