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A role of BMP in the development of glomerular sclerosis.
It has been suggested that, in immunogloblin A (IgA) nephropathy, injury of the podocyte is a key step for the development of glomerular sclerosis. While podocyte damage leads to the development of segmental sclerosis due to the detachment of podocytes from glomerular basement membrane, it can alter the expression level of several secretory molecules expressed in podocytes (e.g. BMP, VEGF or CTGF). Considerable evidences have accumulated to demonstrate that BMP7, a member of the BMP superfamily, attenuates TGFbeta-induced interstitial fibrosis by a reverse of transdifferentiation of renal tubular epithelial cells into mesenchymal cells. BMP is also expressed in the podocytes. Its function, however, is presently not well understood. We generated transgenic mice, which ectopically express noggin, an inhibitor of BMP, only in podocytes. The development of the glomerulus is distinctively affected in some of the transgenic mice showing cystic glomeruli with collapsed capillary tufts (cystic noggin Tg mice). In contrast, the kidney appears to be normal in the other mutants (non-cystic noggin Tg mice). In the latter, however, glomerular sclerosis develops at 10 months of age. F1 mice were obtained from mating F0 non-cystic mice with wild-type mice. Treatment with a low dose antiglomerular basement membrane antibody revealed that the F1 transgenic mice have more severe glomerular sclerosis than the wild-type littermates. In situ hybridization showed that Bmp7, but not Bmp4 is intensely expressed in adult podocytes. In cultured mesangial cells, TGFbeta- induced accumulation of type IV collagen is inhibited by a simultaneous addition of BMP7, but not BMP4. Collectively, therefore, BMP7 can inhibit glomerular sclerosis by regulating matrix metabolism in mesangial cells [1]References
- A role of BMP in the development of glomerular sclerosis. Ueda, H., Miyazaki, Y., Yokoo, T., Utsunomiya, Y., Kawamura, T., Matsusaka, T., Ichikawa, I., Hosoya, T. Nephrology (Carlton, Vic.) (2005)
