Abnormalities of extracellular matrices and transforming growth factor beta1 localization in the kidney of the hereditary nephrotic mice (ICGN strain).

ICR-derived strain with glomerulonephritis (ICGN) is a strain of mice with hereditary nephrotic syndrome with an unidentified cause. Based on histopathological and biochemical data, ICGN mice are considered to be a good experimental model for human idiopathic nephrotic syndrome. In the present study, we histochemically investigated the changes in localization of extracellular matrix (ECM) components and transforming growth factor beta1 (TGF-beta1). Strong immunohistochemical staining of basal membrane ECM components (collagen IV and laminin) and interstitial ECM components (type III collagen and fibronectin) were demonstrated in glomeruli and tubulointerstitum of ICGN mice as compared with those of sex and age-matched ICR mice, used as normal healthy controls. Marked type I collagen and tenascin deposition, which were not detected in the glomeruli of ICR mice, were seen in the glomeruli of ICGN mice. A remarkable increase in active-TGF-beta1 was also detected only in glomeruli of ICGN mice, but not in those of ICR mice. Furthermore, strikingly increased alpha-smooth muscle actin, a marker of activated glomerular mesangial cells, was demonstrated in the glomeruli, mainly in the mesangial cells, of ICGN mice. These findings indicated that ECM components are increased in the glomerulus and tubulointerstitum of ICGN mice, and that active-TGF-beta1 induces such increases in ECM components. The present findings may contribute to elucidation of the pathogenic mechanisms of hereditary nephrotic syndrome in ICGN mice and, in future, human idiopathic nephrotic syndrome.