DECORIN, BIGLYCAN AND THEIR ENDOCYTOSIS RECEPTOR IN RAT RENAL-CORTEX

Background. Among the small proteoglycans, biglycan and decorin have b een proposed to be potent modulators of TGF-beta-mediated inflammatory kidney diseases. They were considered to become induced during glomer ulonephritis and to subsequently inactivate the cytokine. Methods. Dec orin and biglycan as well as their endocytosis receptor were investiga ted in normal rat renal cortex, in anti-Thy-1 glomerulonephritis, in p olycystic kidneys, in the remnant kidney following 5/6-nephrectomy, an d in kidneys from the Milan normotensive strain by immunohistochemistr y and in situ hybridization. Northern blots were used for the detectio n of mRNA expression for decorin and biglycan in isolated glomeruli. F unctional aspects of the endocytosis of decorin and biglycan were stud ied in cultured mesangial cells. Results. In the normal adult rat kidn ey decorin was expressed preferentially by Bowman's capsule and by int erstitial connective tissue cells, but only in trace amounts by mesang ial cells. In contrast, biglycan was found in tubular epithelial cells , in association with glomerular capillaries, podocytes and occasional ly in the mesangium. In the tubulointerstitium of diseased kidneys (po lycystic kidneys, 5/6-nephrectomy, kidneys from the Milan normotensive strain) there was a general up-regulation of decorin expression, whil e biglycan was localized only in distinct foci of fibrotic lesions. Gl omerulosclerosis (5/6-nephrectomy, Milan normotensive strain) was asso ciated with an increased staining for both decorin and biglycan within glomeruli. However, even in the anti-Thy-1 model of an acute mesangio proliferative glomerulonephritis where the greatest accumulation of de corin was found there was only a slight enhancement of decorin mRNA in isolated glomeruli. Decorin and biglycan become degraded upon recepto r-mediated endocytosis. Immunohistochemical investigations indicated t hat the pattern of expression of the receptor protein correlated well with the immunolocalization of both decorin and biglycan. In vitro exp eriments with cultured mesangial cells provided direct evidence for th e expression of the receptor and for the cell's capability to endocyto se decorin as well as biglycan. Conclusions. Decorin and biglycan are characterized by a distinct expression pattern in the normal rat kidne y, whereas the presence of their endocytosis receptor protein correlat es with the expression of both proteoglycans. Decorin is almost comple tely absent in the normal mesangium. Both proteoglycans become up-regu lated in various models of renal disease. The mesangial accumulation o f decorin in the anti-Thy-1 glomerulonephritis that is observed in spi te of the only slightly enhanced mRNA expression could result from dec reased decorin turnover and/or increased mesangial retention.