Activation of gelatinase-tissue-inhibitors-of-metalloproteinase complexes by matrilysin
Activation of gelatinase-tissue-inhibitors-of-metalloproteinase complexes by matrilysin
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DOI：
10.1042/bj3310965
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发表时间：
1998-05-01
影响因子：
4.1
通讯作者：
Nagle, RB
中科院分区：
文献类型：
--
作者：
von Bredow, DC;Cress, AE;Nagle, RB
基质溶酶、明胶酶A和明胶酶B是参与正常和病理过程的基质金属蛋白酶(MMPs)，需要重塑细胞外基质。在人的前列腺组织中，基质溶素在被炎性细胞包围的导管中合成，在前列腺癌中局部合成，但在正常腺体中不合成。明胶酶B的表达仅限于炎性细胞。明胶酶A在良性和恶性前列腺组织中均可发现。基质金属蛋白酶的活性受其从潜伏状态到激活状态的转变以及金属蛋白酶组织抑制物(TIMPs)的存在的调节。我们研究了在它们的结合抑制剂TIMP2和TIMP1分别存在的情况下，基质溶素是否能激活孕激素酶A和B。将孕激素酶B-TIMP1复合体与活性基质溶血素孵育后，通过SDS-PAGE和酶活性测定，分别得到78和68 kDa的活性形式。无TIMP的明胶酶B也可被Matrilysin激活。此外，在佛波酯处理的HT1080细胞的条件培养液中，Matrilysin激活了孕激素酶B，证实了体外实验的结果。相反，基质溶酶不能对明胶酶A-TIMP2复合体进行蛋白水解性切割，而是导致明胶酶原酶的明胶分解活性一过性增加。Matrilysin不能增强自身ProForm的自催化转化。本文提供的数据表明，基质溶素参与了蛋白水解级联反应，并能在TIMP存在的情况下激活明胶酶。
Matrilysin, gelatinase A and gelatinase B are matrix metalloproteinases (MMPs) implicated in normal and pathological processes that require remodelling of the extracellular matrix. In human prostate tissue, matrilysin is synthesized in ducts surrounded by inflammatory cells, and focally in prostate carcinoma, but not in normal glands. Gelatinase B expression is restricted to inflammatory cells. Gelatinase A can be found in both benign and malignant prostate tissue. MMP activities are regulated by their transition from latent to activated forms, as well as by the presence of tissue inhibitors of metalloproteinases (TIMPs). We investigated whether matrilysin can activate progelatinases A and B in the presence of their bound inhibitors TIMP2 and TIMP1 respectively. Incubation of progelatinase B-TIMP1 complex with active matrilysin resulted in 78 and 68 kDa active forms, as measured by SDS-PAGE and enzyme activity assays. TIMP-free gelatinase B was also activated by matrilysin. In addition, activation of progelatinase B by matrilysin was demonstrated in the conditioned medium of phorbol ester-treated HT1080 cells, confirming the results obtained in the in vitro experiments. In contrast, matrilysin did not proteolytically cleave gelatinase A-TIMP2 complex, but led to a transient increase in gelatinolytic activity of the proenzyme. Matrilysin did not enhance the autocatalytic conversion of its own proform. The data presented here suggest that matrilysin participates in a proteolytic cascade and can activate gelatinases in the presence of TIMPs.