Heme oxygenase-1 modulates mesangial cell proliferation by p21 Waf1 upregulation.
Heme oxygenase-1 modulates mesangial cell proliferation by p21 Waf1 upregulation.
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DOI：
10.3109/08860220903491240
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发表时间：
2010-01
期刊：
影响因子：
3
通讯作者：
Singhal PC
中科院分区：
文献类型：
--
作者：
Kumar D;Bhaskaran M;Alagappan L;Tori D;Yadav I;Konkimalla S;Magoon S;Singhal PC
肾小球系膜细胞（MC）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。本研究旨在探讨HO-1在MC增殖中的作用及其分子机制。表皮生长因子（EGF）和肝细胞生长因子（HGF）均能促进系膜细胞HO-1的表达，并促进系膜细胞增殖。有趣的是，HO-1诱导的抑制（通过锌原卟啉，ZnP）。与MC对EGF和HGF的促有丝分裂反应加速有关。HO-1的诱导与系膜细胞p21表达的增强相关。另一方面，血红蛋白和锌磷抑制系膜细胞p21的表达。HO-1对MC生长的影响可能是通过上调p21的表达来介导的。
Mesangial cell (MC) proliferation is a hall mark 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.
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