Cell Surface-Bound Plasminogen Regulates Hepatocyte Proliferation Through a uPA-Dependent Mechanism
Cell Surface-Bound Plasminogen Regulates Hepatocyte Proliferation Through a uPA-Dependent Mechanism
复制标题
DOI：
10.1271/bbb.70126
复制
发表时间：
2007-06
期刊：
影响因子：
--
通讯作者：
Nobuaki Okumura;T. Seki;T. Ariga
中科院分区：
文献类型：
--
作者：
Nobuaki Okumura;T. Seki;T. Ariga
纤溶酶原和纤溶酶原激活剂在肝再生中起重要作用。以前，我们发现纤溶酶原增强大鼠肝细胞原代培养中的肝细胞增殖。在这里，我们研究了外源性纤溶酶原如何影响导致细胞增殖的下游事件。肝细胞中加入纤溶酶原可增加尿激酶型纤溶酶原激活物（uPA）活性，但不影响基质金属蛋白酶（MMP）-9或MMP-2活性。为了提高uPA活性，纤溶酶原需要通过其分子的赖氨酸结合位点与肝细胞表面结合，但uPA mRNA和uPA受体（uPAR）mRNA均不受外源性纤溶酶原的影响。此外，用uPA抑制剂对氨基苯甲脒处理肝细胞，抑制纤溶酶原诱导的甚至EGF诱导的肝细胞增殖。这些结果表明，纤溶酶原相关的控制肝细胞增殖局部产生纤溶亢进状态的细胞表面涉及激活uPA。
Plasminogen and plasminogen activators play important roles in liver regeneration. Previously, we found that plasminogen potentiates hepatocyte proliferation in the primary culture of rat hepatocytes. Here, we examined how exogenous plasminogen affects the downstream events leading to cell proliferation. The addition of plasminogen to hepatocytes increased urokinase-type plasminogen activator (uPA) activity, but did not affect matrix metalloproteinase (MMP)-9 or MMP-2 activities. To increase uPA activity, plasminogen was required to bind the hepatocyte surface through the lysine-binding site of plasminogen molecule, but neither uPA mRNA nor uPA receptor (uPAR) mRNA was affected by the exogenous plasminogen. In addition, treatment of hepatocytes with an uPA inhibitor, p-aminobenzamidine, inhibited the plasminogen-induced and even EGF-induced hepatocyte proliferation. These results suggest that plasminogen-related control of hepatocyte proliferation is exerted topically by producing a hyperfibrinolytic state on the cellular surface involving the activation of uPA.