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首页> 外文期刊>Journal of Cellular Physiology >Plasmin activates pro-matrix metalloproteinase-2 with a membrane-type 1 matrix metalloproteinase-dependent mechanism.
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Plasmin activates pro-matrix metalloproteinase-2 with a membrane-type 1 matrix metalloproteinase-dependent mechanism.

机译：血纤维蛋白溶酶激活pro-matrix metalloproteinase-2膜式1的矩阵metalloproteinase-dependent机制。

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摘要

Membrane-type 1 matrix metalloproteinase (MT1-MMP) has been implicated as a physiological activator of progelatinase A (MMP-2). We previously reported that plasmin treatment of cells results in proMMP-2 activation and increased type IV collagen degradation. Here, we analyzed the role of MT1-MMP in plasmin activation of MMP-2 using HT-1080 cells transfected with MT1-MMP sense or antisense cDNA. Control, vector-transfected cells that expressed endogenous MT1-MMP, and antisense cDNA transfectants with very low levels of MT1-MMP did not activate proMMP-2. Conversely, cells transfected with sense MT1-MMP cDNA expressed high MT1-MMP levels and processed proMMP-2 to 68/66-kDa intermediate activation products. Control cells and MT1-MMP transfectants had much higher levels of cell-associated MMP-2 than antisense cDNA transfectants. Addition of plasmin(ogen) to control or MT1-MMP-transfected cells generated active, 62-kDa MMP-2, but was ineffective with antisense cDNA transfectants. The effect of plasmin(ogen) was prevented by inhibitors of plasmin, but not by metalloproteinase inhibitors, implicating plasmin as a mechanism for proMMP-2 activation independent of the activity of MT1-MMP or other MMPs. Plasmin-mediated activation of proMMP-2 did not result from processing of proMT1-MMP and did not correlate with alpha(v)beta(3) integrin or TIMP-2 levels. Thus, plasmin can activate proMMP-2 only in the presence of MT1-MMP; however, this process does not require the catalytic activity of MT1-MMP.
机译：膜式基质金属蛋白酶1 (MT1-MMP)已经涉及生理激活progelatinase (MMP-2)。报道,细胞胞浆素治疗的结果在proMMP-2激活和IV型增长胶原蛋白降解。血纤维蛋白溶酶激活的MT1-MMP MMP-2使用ht - 1080细胞转染MT1-MMP或感觉反义的互补。表达内源性MT1-MMP,反义互补脱氧核糖核酸水平非常低的转染子MT1-MMP没有激活proMMP-2。细胞转染MT1-MMP cDNA感表示高MT1-MMP水平和处理proMMP-2 68/66-kDa中间激活产品。有更高水平的细胞相关MMP-2吗反义cDNA转染子。血纤维蛋白溶酶(ogen)控制或MT1-MMP-transfected生成细胞活跃,62 kda MMP-2,但是无效的反义cDNA转染子。血纤维蛋白溶酶的影响(ogen)阻止了血纤维蛋白溶酶的抑制剂,但不是金属蛋白酶抑制剂,暗示胞浆素作为一个proMMP-2激活的机制独立于MT1-MMP或其他的活动基质金属蛋白酶。从proMT1-MMP处理,也没有结果不与α(v)β(3)整合素TIMP-2水平。proMMP-2只在MT1-MMP面前;然而,这个过程不需要MT1-MMP的催化活性。

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