Changes in renal glomerular basement membrane with age and nephritis

Abstract

Glomerular basement membrane was obtained from normal, young and old adult rats and from animals with antiserum nephritis, daunomycin nephrosis, and lathyrism. With increased age there was an increase in the collagen content of whole glomeruli and of the basement membrane. About 50% of the membrane protein was solubilized in 1% sodium dodecyl sulfate, and a further 35% was solubilized by reduction and alkylation. Inhibition of formation of collagen cross-links by induction of lathyrism did not affect membrane solubility. Preparative disc gel electrophoresis permitted separation of a number of components of different composition; with decreasing molecular weight the collagen content declined from almost 100% to 0%.In antiserum nephritis, there was an increase in the noncollagen components of the membrane and marked alterations in amino acid composition, both of whole membrane and of electrophoretically separated components. In daunomycin nephrosis, the amino acid composition was similar to that of antiserum nephritis. The solubility of membrane from nephritic rats was normal. The composition of the insoluble residue was similar for all membrane preparations and resembled pure collagen. It is suggested that the presence of abnormal noncollagen proteins, associated with the insoluble collagen core by hydrophobic and disulfide bonds, as in antiserum nephritis, is associated with increased membrane permeability leading to proteinuria.