Transforming growth factor ß1-induced glomerulopathy is prevented by 17ß-estradiol supplementation.

Autor: Camilla Birch Nielsen, Søren Krag, Ruth Østerby, Allan Flyvbjerg, Jens Nyengaard, Axel Forman, Lise Wogensen
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Zdroj: Virchows Archiv: European Journal of Pathology; Jun2004, Vol. 444 Issue 6, p561-566, 6p
Abstrakt: Transforming growth factor ß1 (TGF-ß1) affects extracellular matrix (ECM) accumulation. It plays a role in the thickening of the peripheral basement membrane (PBM) and expansion of the mesangium in several renal diseases. The beneficial influence of female gender on the progression of chronic renal diseases may be explained by a favorable effect of estrogen on ECM homeostasis. Interactions between TGF-ß1 and estrogen have been investigated in mesangial cell cultures. However, it is unknown if TGF-ß1-induced glomerulopathy in vivo is influenced by exogenous estrogen. Thus, the aim of the present experiment was to explore whether estrogen prevents the development of TGF-ß1-induced glomerular disease in transgenic mice expressing active TGF-ß1 under control of the Ren-1 c promoter. Mice were treated from 3 weeks to 6 weeks of age with 17ß-estradiol release pellets (5?10 µg/kg body weight per day). At the age of 6 weeks, all investigated animals were sacrificed for estimation of PBM thickness, the mesangium per glomerulus [Vv(mes/glom)], the mesangial matrix per glomerulus [Vv(matrix/glom)] and the PBM per glomerulus [Vv(PBM/glom)] using electron microscopy and stereological methods. Furthermore, the total collagen content was determined. We found that TGF-ß1-induced alterations in Vv(mes/glom), Vv(matrix/glom) and Vv(PBM/glom) were prevented in mice exposed to exogenous 17ß-estradiol. In addition, the interstitial fibrosis that develops in TGF-ß1 transgenic mice was attenuated by administration of 17ß-estradiol. In conclusion, estrogen may oppress TGF-ß1-mediated kidney diseases and, thereby, contribute to the protracted development of end-stage renal disease in pre-menopausal women. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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