IMMUNOHISTOCHEMICAL LOCALIZATION OF COLLAGEN-VI IN DIABETIC GLOMERULI

Late stage diabetic nephropathy is histologically characterized by eit her diffuse or nodular expansion of the glomerular matrix. This is pre sumed to represent the morphological correlate for the functional impa irment of the kidney. The exact matrix composition of the nodular glom erulosclerosis lesion of end-stage diabetic nephropathy is not known. Biochemical studies have provided evidence that the microfibrillar col lagen type VI is increased in diabetic nephropathy. Consequently, this immunohistochemical study was designed to evaluate the extent and exa ct morphologic location of increased collagen VI deposition at various stages of diabetic glomerulosclerosis (GS). An irregular, sometimes s pot-like staining of collagen VI was observed in diffuse GS in the mes angial portion. The uninterrupted staining which was evident along the glomerular basement membrane in normal glomeruli was discontinuous in diffusely sclerotic glomeruli. In nodular GS, the markedly increased deposition of collagen VI appeared to be evenly distributed throughout the entire nodular lesion. At the same time, mesangial staining for c ollagen IV was reduced in nodular GS, suggesting that in the expanded mesangial matrix collagen IV is progressively substituted by collagen VI during the transition from diffuse to nodular GS. The colocalizatio n of PAS staining with collagen VI deposition in nodular GS suggests t hat the typical Kimmelstiel-Wilson lesions at least in part consist of collagen VI. Biochemical analysis confirmed the increased collagen VI deposition in glomeruli extracted from diabetic patients with nodular GS. Application of two antisera, recognizing primarily the alpha 1(VI )- and alpha 2(VI)-chains and the N-terminal part of alpha 3(VI)-chain , respectively, revealed no difference in staining pattern. Comparison of the immunohistochemical results with clinical parameters of diabet ic nephropathy suggested that increasing collagen VI deposition may be an indicator of the irreversible remodeling of the glomerular matrix to nodular GS which is associated with functional insufficiency. Our f indings indicate striking differences of the mesangial matrix composit ion in diffuse and nodular GS. These observations together with earlie r results provide evidence for a ''switch'' in the matrix protein prod uction in association with the development of nodular GS in diabetic n ephropathy.