Mesangial cell proteoglycans: synthesis and metabolism.

Abstract

In cultures of human adult glomerular mesangial cells, large chondroitin sulfate proteoglycans (CSPG) and small dermatan sulfate proteoglycans (DSPG) are synthesized. The large CSPG has a core protein, M(r) of 400,000 (major) and M(r) of 500,000 (minor), and binds to hyaluronic acid to form large aggregates. The two small DSPGs (Mr of approximately 350,000 and M(r) of approximately 200,000) were related to biglycan and decorin, respectively. The majority of these proteoglycans were located in the culture medium, but a hydrophobic form of the CSPG was extracted from the cell layer. Mesangial cells in the growing phase synthesized and secreted all three types of proteoglycans, but in cells arrested in G0 by serum deprivation the incorporation of (35S)sulfate in CSPG was drastically reduced. In the same cells stimulated to proliferate by replacing the medium with one containing serum, the synthesis of CSPG dramatically enhanced. The synthesis of CSPG and DSPG was also elevated in cells cocultured with cytokines but in contrast was significantly reduced when cultured in medium containing hyperglycemic levels of glucose. Finally, preliminary experiments are reported that indicate that CSPG and DSPG bind to low-density lipoproteins in vitro. These observations suggest a possible specialized function for proteoglycans in cellular processes characteristic of glomerular disease.