Distribution of de novo synthesized sulfated glycosaminoglycans in the glomerular basement membrane and mesangial matrix.

Abstract

The distribution of de novo synthesized heparan sulfate-glycosaminoglycan (GAG) and chondroitin sulfate-GAG of the mesangial matrix and the glomerular basement membrane was determined by a combination of biochemical and autoradiographic methods. The de novo synthesized sulfated GAGs were labeled by the ex situ organ perfusion of kidneys with [35S]sulfate for periods of time up to 7 hours. Biochemical analysis of a combined extract of the matrices revealed that both heparan sulfate-GAG and chondroitin sulfate-GAG are present at levels of approximately 90 and 10%, respectively, and that these relative levels do not change with increasing organ perfusion times. Autoradiographic analysis of the de novo synthesized sulfated GAGs in each of the matrices showed that the mesangial matrix incorporated two to three times as much of the sulfated GAGs as the glomerular basement membrane. The predominant GAG in both the matrices was heparan sulfate-GAG and chondroitin sulfate-GAG was exclusively present in the mesangial matrix, thereby indicating that these two matrices are compositionally different. These differences may be of some importance in the establishment of normal glomerular function and organization and in the alteration of that function and organization as a result of various disease processes, possibly those that are immune complex mediated.