Activated protein C stimulates proliferation, migration and wound closure, inhibits apoptosis and upregulates MMP-2 activity in cultured human keratinocytes
Activated protein C stimulates proliferation, migration and wound closure, inhibits apoptosis and upregulates MMP-2 activity in cultured human keratinocytes
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DOI：
10.1016/j.yexcr.2004.05.015
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发表时间：
2004-09-10
影响因子：
3.7
通讯作者：
Jackson, C
中科院分区：
文献类型：
--
作者：
Xue, ML;Thompson, P;Jackson, C
活化蛋白C(APC)是一种调节血液凝结和炎症的生理性丝氨酸蛋白酶。角质形成细胞是人类皮肤的一种主要细胞类型，在皮肤的正常代谢和皮肤创面愈合中起着重要的作用。在这项研究中，我们研究了APC对原代培养的人角质形成细胞功能的调节作用。在体外损伤实验中，APC通过促进细胞的增殖和迁移而加速了伤口的愈合。APC通过阻止细胞凋亡来减轻钙诱导的细胞死亡，caspase-3活性和形态上的凋亡细胞均减少。APC可显著增强角质形成细胞表达和激活基质金属蛋白酶-2，而对基质金属蛋白酶-9无影响。GM6001是一种广谱的基质金属蛋白酶抑制剂，以剂量依赖的方式抑制细胞迁移，并延迟体外伤口愈合。APC还可显著增加IL-6和IL-8的产生，抑制钙和内毒素刺激的NF-kappaB活性。这些结果表明，在培养的角质形成细胞中，APC在促进细胞增殖和迁移、防止细胞凋亡和增加基质金属蛋白酶-2活性方面起着中心作用。这一调节活动表明，APC在伤口愈合过程中具有促进再上皮化的潜力。(C)2004 Elsevier Inc.保留所有权利。
Activated protein C (APC) is a physiological serine protease that regulates-blood clotting and inflammation. Keratinocytes are a major cell type of human skin and play a fundamental role in normal skin metabolism and cutaneous wound healing. In this study, we investigated the regulatory role of APC on the function of human primary cultured keratinocytes, In an in vitro wounding assay, APC accelerated wound closure which was due jointly to increased cell proliferation and migration. APC attenuated calcium-induced cell death via prevention of cell apoptosis, as indicated by a decrease in both active caspase-3 and morphologically apoptotic cells. APC dramatically enhanced the expression and activation of MMP-2 by keratinocytes, whilst having no effect on MMP-9. GM6001, a broad spectrum MMP inhibitor, abolished cell migration in a dose-dependent manner and delayed in vitro wound healing. APC also significantly increased the production of IL-6 and IL-8 and suppressed calcium- and LPS-stimulated NF-kappaB activity. These results demonstrate a central role for APC in promoting cell proliferation and migration, preventing apoptosis and increasing MMP-2 activity in cultured keratinocytes. This regulatory activity implicates APC as having potential to promote re-epithelialisation during wound healing. (C) 2004 Elsevier Inc. All rights reserved.