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首页> 外文期刊>Cytokine >FK506, transforming growth factor-beta1 and mesangial matrix synthesis: parallels and differences compared with cyclosporine A.
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FK506, transforming growth factor-beta1 and mesangial matrix synthesis: parallels and differences compared with cyclosporine A.

机译：FK506，转化生长因子-beta1和肾小球系膜基质合成：与环孢霉素A的相似之处和不同之处。

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Cyclosporine A (CsA)-induced glomerulosclerosis is a well-described side effect of CsA treatment. Current evidence indicates that FK506 causes similar morphologic changes. Recently, we demonstrated that CsA up-regulates the expression of transforming growth factor-beta1 (TGF-beta1), its receptors type I (TbetaR-I) and type II (TbetaR-II), as well as related matrix protein synthesis in mesangial cells (MCs). Here, we assessed the effect of FK506 on the expression of TGF-beta1, TbetaR-I, TbetaR-II, fibronectin (FN) and plasminogen activator inhibitor type-1 (PAI-1) in MCs. Resting MCs were incubated with/without FK506. Time- and concentration-dependent expression was measured at the mRNA and protein level. Compared to untreated controls, FK506 stimulated TGF-beta1 mRNA (maximum at 8 h, 100 ng/mL: 2.13+/-0.15-fold, P<0.005) and protein expression (maximum at 96 h, 100 ng/mL: 1.96+/-0.29-fold, P<0.005). In contrast, TbetaR-I and TbetaR-II protein expression remained unchanged. Concerning matrix protein synthesis, FK506 slightly increased FN production (96 h, 100 ng/mL: 1.38+/-0.28-fold, P<0.05), but not PAI-1 production. These results indicate that, comparable to CsA, FK506 induced glomerulosclerosis is also due to a direct effect on mesangial matrix production, which is at least in part mediated via up-regulation of TGF-beta1 expression. The fact that, unlike CsA, FK506 does not increase the expression of TbetaR-I, TbetaR-II, and PAI-1, deserves further investigation.
机译：环孢菌素A（CsA）诱导的肾小球硬化症是CsA治疗的众所周知的副作用。目前的证据表明FK506会引起类似的形态变化。最近，我们证明CsA上调肾小球系膜中转化生长因子-beta1（TGF-beta1），其受体I（TbetaR-I）和II（TbetaR-II）的表达，以及相关基质蛋白的合成单元（MC）。在这里，我们评估了FK506对MC中TGF-beta1，TbetaR-I，TbetaR-II，纤连蛋白（FN）和纤溶酶原激活物抑制剂1型（PAI-1）表达的影响。将静止的MC与/不与FK506一起孵育。在mRNA和蛋白质水平上测量时间和浓度依赖性表达。与未处理的对照组相比，FK506刺激了TGF-beta1 mRNA（最大8h，100 ng / mL：2.13 +/- 0.15倍，P <0.005）和蛋白质表达（最大96h，100 ng / mL：1.96+） /-0.29倍，P <0.005）。相反，TbetaR-I和TbetaR-II蛋白表达保持不变。关于基质蛋白的合成，FK506略微增加了FN的产生（96 h，100 ng / mL：1.38 +/- 0.28倍，P <0.05），但不增加PAI-1的产生。这些结果表明，与CsA相比，FK506诱导的肾小球硬化症还直接影响肾小球系膜基质的产生，这至少部分是由TGF-β1表达的上调介导的。与CsA不同，FK506不增加TbetaR-I，TbetaR-II和PAI-1的表达，这一事实值得进一步研究。

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