Effects of decidua-conditioned medium and insulin-like growth factor binding protein-1 on trophoblastic matrix metalloproteinases and their inhibitors

Effects of decidua-conditioned medium and insulin-like growth factor binding protein-1 on trophoblastic matrix metalloproteinases and their inhibitors
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DOI:
10.1016/s0143-4004(98)91038-4
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发表时间:
1998-09-01
期刊:
影响因子:
3.8
通讯作者:
Tseng, L
Tseng, L
中科院分区:
医学3区
文献类型:
--
作者:
Bischof, P;Meisser, A;Tseng, L

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研究体外蜕膜基质细胞(DESCM)及其主要分泌产物胰岛素样生长因子结合蛋白-1(IGFBP-1)对滋养层明胶酶和金属蛋白酶组织抑制剂(TIMP-1)分泌的调节作用。早孕期细胞滋养细胞 (CTB) 获自流产,并在存在或不存在 DESCM 或 IGFBP-1 的情况下进行体外培养。通过酶谱法和总明胶分解活性的测量来分析培养物上清液中分泌的明胶酶。通过市售免疫测定法测量 TIMP-1、hCG 和胎儿纤连蛋白 (fFN)。 DESCM 抑制 CTB 的总明胶分解活性,但增加滋养层 MMP-9、TIMP-1 和 fFN。相反,IGFBP-1增加总明胶分解活性和TIMP-1,对MMP-2、MMP-9或fFN没有影响,但抑制hCG。结论是蜕膜细胞分泌的一种因子通过增加TIMP-1来抑制滋养层的明胶分解特性。其他尚未确定的蜕膜因子会增加 MMP-2 和 MMP-9 的水平,从而超越 TIMP-1 的抑制作用。由于与 DESCM 相比,IGFBP-1 增加了 CTB 的总明胶分解活性,因此它不能是调节 CTB 蛋白水解活性的主要活性蜕膜因子。讨论了 IGFBP-1 整合素介导的 CTB 作用的可能性。 (C) 1998 W. B. 桑德斯有限公司
The regulatory role of in vitro decidualized stromal cells (DESCM) and their main secretory product insulin-like growth factor binding protein-1 (IGFBP-1) was studied on the secretion of trophoblastic gelatinases and tissue inhibitor of metalloproteinase (TIMP-1). First trimester cytotrophoblastic cells (CTB) were obtained from abortions and cultured in vitro in presence or absence of DESCM or IGFBP-1. Secreted gelatinases were analysed in the culture supernatants by zymography and by measurements of the total gelatinolytic activity. TIMP-1, hCG, and fetal fibronectin (fFN) were measured by commercially available immunoassays. DESCM inhibited the total gelatinolytic activity of CTB but increased trophoblastic MMP-9, TIMP-1 and fFN. In contrast, IGFBP-1 increased the total gelatinolytic activity and TIMP-1, had no effect on MMP-2, MMP-9 or fFN but inhibited hCG. It is concluded that a factor secreted by decidual cells inhibits the gelatinolytic property of trophoblast by increasing TIMP-1. Other decidual factors, as yet unidentified, increase MMP-2 and MMP-9 to an extent which does override the inhibitory effect of TIMP-1. Since in contrast to DESCM, IGFBP-1 increases the total gelatinolytic activity of CTB, it cannot be the primary active decidual factor regulating the proteolytic activity of CTB. The possibility of an integrin-mediated effect of IGFBP-1 on CTB is discussed. (C) 1998 W. B. Saunders Company Ltd.