Heparan sulfate stimulates extracellular matrix protein synthesis by mesangial cells in culture

Heparan sulfate, a glycosaminoglycan which is a component of the glomerular basement membrane and the mesangial matrix, has been demonstrated to inhibit mesangial cell growth. The present studies investigated the effects of heparan sulfate on extracellular matrix protein synthesis by cultured rat mesangial cells. Mesangial cells were metabolically labeled with 35S-methionine and specific extracellular matrix proteins were immunoprecipitated from supernatant and cellular fractions. The following extracellular proteins were assayed: type I collagen, type IV collagen, type V collagen, laminin and fibronectin. Western blotting was performed to demonstrate the specificity of the immunoprecipitates. Heparan sulfate decreased cell number by 23.5%, p < 0.05, while chondroitin sulfate, another glycosaminoglycan, increased cell number by 11.5%, p < 0.05. Heparan sulfate significantly increased type V collagen and laminin in the cellular material and significantly increased laminin and fibronectin in the supernatant material. Chondroitin sulfate had no effect on matrix protein synthesis. Thus, heparan sulfate has effects on both mesangial cell growth and synthesis of matrix proteins and alterations in heparan sulfate may play a role in the development of glomerulosclerosis.