Regulation of ProMMP-1 and ProMMP-3 activation by tissue factor pathway inhibitor-2/matrix-associated serine protease inhibitor
Regulation of ProMMP-1 and ProMMP-3 activation by tissue factor pathway inhibitor-2/matrix-associated serine protease inhibitor
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DOI：
10.1006/bbrc.1999.0153
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发表时间：
1999-02-05
影响因子：
3.1
通讯作者：
Rao, JS
中科院分区：
文献类型：
--
作者：
Rao, CN;Mohanam, S;Rao, JS
组织因子途径抑制剂-2（TFPI-2）/基质相关丝氨酸蛋白酶抑制剂（MSPI）是一种32至33 kDa的Kunitz型丝氨酸蛋白酶抑制剂，可抑制纤溶酶和胰蛋白酶。由于纤溶酶和胰蛋白酶参与前基质金属蛋白酶proMMP-1和proMMP-3的活化，我们研究了TFPI-2/MSPI在这些酶原活化中的作用。纤溶酶和胰蛋白酶通过将53 kDa酶原转化为部分活性的43 kDa多肽来激活proMMP-1; TFPI-2/MSPI抑制这种活性。类似地，TFPI-2/MSPI抑制66-kDa proMMP-3通过纤溶酶和胰蛋白酶转化为活化的45-和30-kDa多肽。由于纤溶酶参与proMMP-3的生理激活，我们测试了TFPI-2/MSPI是否抑制HT-1080纤维肉瘤细胞和尿激酶荷电HeLa细胞对proMMP-3的激活。我们发现，抑制剂抑制前MMP-3激活HT-1080细胞和尿激酶充电HeLa细胞。总的来说，我们的研究结果表明，TFPI-2/MSPI间接调节MMP-1和MMP-3催化的基质蛋白水解，通过调节proMMP-1和proMMP-3的激活。(C)北京：科学出版社.
Tissue factor pathway inhibitor-2 (TFPI-2)/matrix-associated serine protease inhibitor (MSPI), a 32- to 33-kDa Kunitz-type serine protease inhibitor, inhibits plasmin and trypsin. Because plasmin and trypsin are involved in the activation of promatrix metalloproteases proMMP-1 and proMMP-3, we investigated the role of TFPI-2/MSPI in the activation of these proenzymes. Both plasmin and trypsin activated proMMP-1 by converting the 53-kDa proenzyme to the partially active 43-kDa polypeptide; this activity was inhibited by TFPI-2/MSPI. Similarly, TFPI-2/MSPI inhibited the conversion of 66-kDa proMMP-3 to the activated 45- and 30-kDa polypeptides by plasmin and trypsin. Because plasmin is involved in the physiological activation of proMMP-3, we tested whether TFPI-2/MSPI inhibits the activation of proMMP-3 by HT-1080 fibrosarcoma cells and urokinase-charged HeLa cells. We found that the inhibitor inhibited proMMP-3 activation by HT-1080 cells and urokinase-charged HeLa cells. Collectively, our results suggest that TFPI-2/MSPI indirectly regulates MMP-1- and MMP-3-catalyzed matrix proteolysis by regulating the activation of proMMP-1 and proMMP-3. (C) 1999 Academic Press.