HEPARIN MODULATES PROLIFERATION AND PROTEOGLYCAN BIOSYNTHESIS IN MURINE MESANGIAL CELLS - MOLECULAR CLUES FOR ITS ACTIVITY IN NEPHROPATHY

Glycosaminoglycan administration has favourable effects on morphologic al and functional renal abnormalities in different models. The possibi lity that exogenous glycosaminoglycans modulate glomerular matrix synt hesis was explored in both primary and SV40-MES13 murine mesangial cel l cultures. On both cell types, both low-molecular-weight heparin and different glycosaminoglycans showed dose-dependent inhibition of proli feration and increase of (SO42-)-S-35 uptake. After 36 h the cell comp artment contained a spectrum of S-35-molecules of less than 200 kDa; u nder heparin treatment, the two main (SO42-)-S-35 components (high and medium MW) increased by 16 and 37% respectively. Susceptibility to gl ycosidases revealed that heparin promotes the expression of heparan su lphate and increases that of chondroitin sulphate. Moreover, heparin m odifies the expression of decorin and biglycan, involved in adhesion a nd fibrillogenesis, while not affecting perlecan. The extracellular ma trix modulation in renal cells, for which the sulphation type and rati o of heparin are crucial, may thus explain the beneficial renal effect s of heparin.