Occurrence of type VI collagen in extracellular matrix of renal glomeruli and its increase in diabetes.

Human and bovine glomerular basement membrane (GBM) preparations, representing the extracellular matrix of the renal filtration units, were found to contain type VI collagen. This protein was solubilized by guanidine and guanidine-dithiothreitol extractions and characterized after polyacrylamide gel electrophoretic resolution by immunoblotting with an antiserum directed against the alpha 1(VI) and alpha 2(VI) polypeptide chains and by its insensitivity to collagenase digestion in the nonreduced state. In contrast to GBM, which is the product of three distinct cells, type VI collagen could not be detected in extracts from calf lens capsule, an epithelial cell-derived basement membrane. Quantitation by radioimmunoassay of the type VI collagen content of GBM from 17 diabetic and 15 nondiabetic human subjects indicated a 2.8-fold higher level (P less than 0.001) in the diabetic preparations. Because in the glomerulus type VI collagen is considered on the basis of immunohistochemistry to be localized to the mesangium, we believe that measurement of this protein in GBM preparations can provide a valuable index of mesangial expansion in diabetic and other glomerulopathies.