Nephrol Dial Transplant (2000) 15: 167-172
© 2000 European Renal Association-European Dialysis and Transplant Association
Low-density lipoprotein stimulates mesangial cell proteoglycan and hyaluronan synthesis
University of Wales College of Medicine, Institute of Nephrology, Heath Park, Cardiff, UK
Correspondence and offprint requests to: Professor Malcolm Davies, University of Wales College of Medicine, Institute of Nephrology, Heath Park, Cardiff CF11 4XN, UK. E-mail: daviesm6{at}cardiff.ac.uk.
Background. Hyperlipidaemia leads to glomerulosclerosis in small mammals and may contribute to progressive renal disease in man. One prominent feature of lipid-induced glomerular injury in animal models is the accumulation of mesangial matrix. These studies were designed to investigate whether low-density lipoprotein (LDL) enhanced mesangial cell (MC) matrix deposition by modulating the production of proteoglycans (PG) and hyaluronan (HA).
Methods. Growth arrested human MC were metabolically labelled with either 50 µCi/ml Na2[35S]sulphate or 25 µCi/ml [3H]glucosamine and stimulated with LDL (10–100 µg/ml). The radiolabelled PG and HA extracted from the cell layer and the culture medium were isolated, quantified and characterized. Comparison of the PG core proteins synthesized by MC was carried out using Western blot analysis.
Results. LDL stimulation led to a dose- and time-dependent increase in [35S]sulphate incorporation into PG in the culture medium and to a lesser extent in the cell layer. Analysis of the glycosaminoglycan (GAG) chains showed no difference in either their size or charge. Enzyme digestion studies demonstrated that the synthesis of both chondroitin sulphate PG (CSPG) and heparan sulphate PG (HSPG) was enhanced as was the production of the core proteins of versican (a large CSPG), perlecan (a basement membrane HSPG) and to a lesser extent decorin (a small dermatan sulphate PG (DSPG)). An increase in HA synthesis was also demonstrated in [3H]glucosamine labelled cells following LDL stimulation.
Conclusion. LDL selectively enhances the synthesis of specific PG and HA by mesangial cells. Such effects may contribute to the expansion of the mesangial matrix and modify cell-matrix interactions in lipid-induced renal damage.
Keywords: glomerulosclerosis; hyaluronan; lipid; low-density lipoprotein; mesangial cell; proteoglycans
* Present address: Department of Nephrology, University Hospital (Birmingham) NHS Trust, Queen Elizabeth Hospital, Birmingham B15 2TH, UK.
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  S. Kastner, G. J. Thomas, R. H. Jenkins, M. Davies, and R. Steadman Hyaluronan Induces the Selective Accumulation of Matrix- and Cell-Associated Proteoglycans by Mesangial Cells Am. J. Pathol., December 1, 2007; 171(6): 1811 - 1821. [Abstract] [Full Text] [PDF]
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