Small proteoglycans of normal adult human kidney: Distinct expression patterns of decorin, biglycan, fibromodulin, and lumican

Background Among the members of the small leucine-rich proteoglycan family, decorin, biglycan, and fibromodulin have been proposed to be potent modula tors of transforming growth factor-beta (TGF-beta) activity, thereby playin g an important role in the pathogenesis of fibrotic kidney diseases. Furthe rmore, decorin expression influences the expression of p21(WAF1/CIP1) which has been related to kidney hypertrophy and hyperplasia. However, none of t he members of this proteoglycan family have been investigated in normal adu lt human kidney cortex, thus making it impossible to correlate disease-medi ated alterations of their expression with the normal situation in vivo. Methods. The chondroitin/dermatan sulfate proteoglycans, decorin and biglyc an, and the keratan sulfate proteoglycans, fibromodulin and lumican, were i nvestigated in normal human adult renal cortex by immunohistochemistry on t he light and electron microscopic level and by in situ hybridization. North ern blot and reverse transcription-polymerase chain reaction (RT-PCR) metho ds were used to get an estimate of their expression in isolated glomeruli. Decorin excretion with the urine was measured by Western blotting. Results. Two bands of decorin and a single band of biglycan mRNA were ident ified in Northern blots of isolated glomeruli. Amplification by RT-PCR was required to detect the signals for fibromodulin and lumican. All four prote oglycans were preferentially expressed in the renal interstitium with accum ulations around tubules. Weak expression was found in the mesangial matrix. Biglycan was expressed by glomerular endothelial cells and, together with fibromodulin, was synthesized and deposited in distal tubular cells and col lecting ducts. Immunogold labeling indicated the presence of the proteoglyc ans in the glomerular basement membrane, which was interpreted as a result of glomerular filtration. Indirect evidence suggested tubular reuptake of d ecorin after glomerular filtration. Conclusion. The data indicate that the different cells of the adult human k idney are characterized by a distinct expression pattern of the four small proteoglycans. It is suggested that these proteoglycans may have distinct p athophysiological roles depending upon whether they are expressed by mesang ial cells, endothelial cells, epithelial cells, or cells of the tubulointer stitium.