Fujigaki Y, Watanabe T, Ikegaya N, Yonemura K, Sun D F, Hishida A, Yamamoto T, Kojima K, Nagase M
First Department of Medicine, Hamamatsu University School of Medicine, Japan.
Nephrol Dial Transplant. 2000 Feb;15(2):191-9. doi: 10.1093/ndt/15.2.191.
Transforming growth factor (TGF)-beta is a regulator of extracellular matrix accumulation. Both TGF-beta receptors, type I (TbetaRI) and type II (TbetaRII), may be required for signal transduction in the TGF-beta pathway. The aim of this study was to investigate the relationship between the TGF-beta pathways and glomerular basement membrane (GBM) accumulation in vivo.
We examined TbetaRI, II, and III protein expression on visceral glomerular epithelial cells (GEP) in relation to GBM alterations in passive Heymann nephritis (PHN), anti-GBM nephritis and anti-thymocyte serum (ATS) nephritis. Renal tissues were examined by pre-embedding immunoelectron microscopy 3, 7 and 14 days after induction of nephritis in rats.
In normal control rats TbetaRI was not detected on GEP, TbetaRII expression was very occasionally found on GEP and TbetaRIII was seen in the cytoplasm of the GEP. TbetaRI, TbetaRII, and TbetaRIII were constitutively expressed on glomerular endothelial cells. By day 3 of anti-GBM nephritis and PHN, expression of TbetaRI, TbetaRII, and TbetaRIII was still similar to that of normal control rats, and GBM alterations in both models were not prominent except for deposit formation in PHN. From day 7 onwards, in both models, expression of TbetaRI and TbetaRII on GEP increased in association with GBM thickening. Expression of TbetaRIII in the cytoplasm of the GEP was increased, with occasional positive staining being seen on the urinary surface of the GEP from day 7 onwards. On the other hand, at day 3 of ATS nephritis, increased expression of TbetaRI and TbetaRII on GEP was noted, but from day 7 onwards, expression of TbetaR II on GEP dramatically decreased. Expression of TbetaRIII in the cytoplasm of the GEP also transiently increased at day 3. GBM thickening was not noted in ATS nephritis.
The results suggest that persistent upregulation of expression of TbetaRI, TbetaRII and possibly TbetaRIII on GEP may contribute to GBM matrix accumulation in vivo.
转化生长因子（TGF）-β是细胞外基质积聚的调节因子。TGF-β信号转导可能需要I型（TβRI）和II型（TβRII）两种TGF-β受体。本研究旨在探讨体内TGF-β信号通路与肾小球基底膜（GBM）积聚之间的关系。
我们检测了被动型Heymann肾炎（PHN）、抗GBM肾炎和抗胸腺细胞血清（ATS）肾炎中，肾小球脏层上皮细胞（GEP）上TβRI、II和III蛋白表达与GBM改变的关系。在大鼠诱发肾炎后3、7和14天，通过包埋前免疫电子显微镜检查肾组织。
在正常对照大鼠中，未在GEP上检测到TβRI，偶尔在GEP上发现TβRII表达，在GEP的细胞质中可见TβRIII。TβRI、TβRII和TβRIII在肾小球内皮细胞上组成性表达。在抗GBM肾炎和PHN的第3天，TβRI、TβRII和TβRIII的表达仍与正常对照大鼠相似，除PHN中有沉积物形成外，两种模型中的GBM改变均不明显。从第7天起，在两种模型中，GEP上TβRI和TβRII的表达随着GBM增厚而增加。GEP细胞质中TβRIII的表达增加，从第7天起，在GEP的尿表面偶尔可见阳性染色。另一方面，在ATS肾炎的第3天，注意到GEP上TβRI和TβRII的表达增加，但从第7天起，GEP上TβRII的表达急剧下降。GEP细胞质中TβRIII的表达在第3天也短暂增加。ATS肾炎中未观察到GBM增厚。
结果表明，GEP上TβRI、TβRII以及可能的TβRIII表达的持续上调可能在体内导致GBM基质积聚。
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