Molecular architecture and gene expression of glomerular extracellular matrix.

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We observed the normal kidneys and kidneys of diabetic nephropathy and membranous nephropathy patients showing nephrotic syndrome by newly devised "tissue negative staining method" established by Z.Ota, principal investigator. In normal kidneys, glomerular basement membrane (GBM) showed fine meshwork structure consisted of fibrils, and pore size was 2-3nm. In nephrotic patients, pore size was increased and tunnel-like structures (named nephrotic tunnel) with 20-100 nm diameter, which penetrate GBMs from capillary lumen to urinaru lumen. The diameter of this nephrotic tunnel is larger than the albumin molecules, and thus this structure is tightly related to the etiology of the nephrotic syndrome.By ultra-high resolution scanning electron microscopy, we observed the isolated GBM and glomeruli treated with detergent. Furthermore, we investigated the components of the GBMs, by immunoelectron microscopy using the specific antibodies against type IV collagen, hepara sulfate proteoglycans and fibronectins. The GBM was mainly consisted of type IV collagens and three dimentional meshwork.In various forms of glomerulonephritis, the expression of integrins were investigated by immunohistochemistry. In IgA nephropathy, membranous proliferative glomerulonephritis, and lupus nephritis, beta1 integrins and alphav-related receptors were upregulated in the glomeruli. The ligands of integrins, i.e.finronectin, vitronectin and type IV collagens were also increased in the glomeurli. These results indicated that integrin may be involved in the progression of mesangial proliferative glomerulonephritis.