Heparin modulates proliferation and proteoglycan biosynthesis in murine mesangial cells: molecular clues for its activity in nephropathy

Glycosaminoglycan administration has favourable effects on morphologicaland functional renal abnormalities in different models. Thepossibility that exogenous glycosaminoglycans modulate glomerularmatrix synthesis was explored in both primary and SV40-MES13murine mesangial cell cultures. On both cell types, both low-molecular-weightheparin and different glycosaminoglycans showed dose-dependentinhibition of proliferation and increase of ³⁵SO^2–₄ uptake.After 36 h the cell compartment contained a spectrum of ³⁵S-moleculesof less than 200 kDa; under heparin treatment, the two main³⁵SO^2–₄ components (high and medium MW) increased by 16and 37% respectively. Susceptibility to glycosidases revealedthat heparin promotes the expression of heparan sulphate andincreases that of chondroitin sulphate. Moreover, heparin modifiesthe expression of decorin and bigly-can, involved in adhesionand fibrillogenesis, while not affecting perlecan. The extracellularmatrix modulation in renal cells, for which the sulphation typeand ratio of heparin are crucial, may thus explain the beneficialrenal effects of heparin.