血红素加氧酶-1 通过上调 p21 Waf1 调节系膜细胞增殖。
Heme oxygenase-1 modulates mesangial cell proliferation by p21 Waf1 upregulation.
机构信息
Department of Medicine, North Shore University Hospital Manhasset and Long Island Jewish Medical Center, New Hyde Park, New York, USA.
出版信息
Ren Fail. 2010 Jan;32(2):254-8. doi: 10.3109/08860220903491240.
Abstract
Mesangial cell (MC) proliferation is a hallmark of many progressive renal diseases. Heme oxygenase-1 (HO-1) has been shown to have an anti-proliferative effect on vascular smooth muscle cells. In the present study, we evaluated the role of HO-1 on MC proliferation and the involved molecular mechanism. Both epidermal growth factor (EGF) and hepatocyte growth factor (HGF) not only enhanced mesangial cell HO-1 expression but also stimulated proliferation of MCs. Interestingly, inhibition of HO-1 induction (by zinc protoporphyrin, ZnP) was associated with an accelerated mitogenic response to EGF and HGF in MCs. Induction of HO-1 was associated with enhanced mesangial cell p21 expression. On the other hand, hemoglobin and ZnP inhibited mesangial cell p21 expression. It appears that the effect of HO-1 on MC growth may be mediated through upregulation of p21 expression.
摘要
系膜细胞增殖是许多进行性肾脏疾病的标志。血红素加氧酶-1（HO-1）已被证明对血管平滑肌细胞具有抗增殖作用。在本研究中，我们评估了 HO-1 在系膜细胞增殖中的作用及其涉及的分子机制。表皮生长因子（EGF）和肝细胞生长因子（HGF）不仅增强了系膜细胞 HO-1 的表达，还刺激了 MC 的增殖。有趣的是，HO-1 诱导的抑制（通过锌原卟啉，ZnP）与 MC 中对 EGF 和 HGF 的有丝分裂反应加速有关。HO-1 的诱导与系膜细胞 p21 表达的增强有关。另一方面，血红蛋白和 ZnP 抑制系膜细胞 p21 的表达。HO-1 对 MC 生长的影响似乎可以通过上调 p21 表达来介导。
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