Inhibition of trophoblast cell invasion by TGFB1, 2, and 3 is associated with a decrease in active proteases
Inhibition of trophoblast cell invasion by TGFB1, 2, and 3 is associated with a decrease in active proteases
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DOI：
10.1095/biolreprod.105.040337
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发表时间：
2005-08-01
影响因子：
3.6
通讯作者：
Robson, SC
中科院分区：
文献类型：
--
作者：
Lash, GE;Otun, HA;Robson, SC
在人类妊娠中，绒毛外滋养层细胞侵入子宫受到严格的调控。转化生长因子-β（TGFB）家族已被认为在控制这一过程中发挥作用。我们假设TGFBI、2和3将抑制绒毛外滋养层细胞的侵袭能力。我们还研究了滋养层细胞凋亡和增殖和分泌的蛋白酶水平作为这些细胞因子可能发挥作用的潜在机制。用中和抗体抑制内源性TGFB 1、2和3增加了胎盘外植体来源的绒毛外滋养层细胞的侵袭能力。类似地，添加外源性TGFBI、2和3以剂量依赖性方式抑制这些细胞的侵袭能力。胎盘外植体中滋养层的增殖并未因任何测试的细胞因子而改变。绒毛和绒毛外滋养层细胞的凋亡没有改变TGFB 1，2和3。基质金属蛋白酶（MMP）9和尿激酶纤溶酶原激活剂的分泌水平降低，对所有三种细胞因子的反应。MMP 2和金属蛋白酶组织抑制剂1和3水平没有改变。这些结果表明，TGFB 1，2，和3抑制滋养层细胞的侵袭依赖于降低蛋白酶活性的机制。
Invasion of extravillous trophoblast cells into the uterus in human pregnancy is tightly regulated. The transforming growth factor-beta (TGFB) family has been suggested to play a role in controlling this process. We hypothesized that TGFBI, 2, and 3 would inhibit the invasive capacity of extravillous trophoblast cells. We also studied trophoblast apoptosis and proliferation and secreted protease levels as potential mechanisms by which these cytokines may act. Inhibition of endogenous TGFB1, 2, and 3 with neutralizing antibodies increased the invasive capacity of extravillous trophoblast cells derived from placental explants. Similarly, addition of exogenous TGFBI, 2, and 3 inhibited the invasive capacity of these cells in a dose-dependent manner. Proliferation of trophoblast in the placental explants did not alter in response to any of the cytokines tested. Apoptosis of villous and extravillous trophoblast did not alter in response to TGFB1, 2, and 3. There was a reduction in secreted levels of matrix metalloproteinase (MMP) 9 and urokinase plasminogen activator in response to all three cytokines. MMP2 and tissue inhibitor of metal loproteinase 1 and 3 levels were not altered. These results suggest that TGFB1, 2, and 3 inhibit trophoblast invasion by a mechanism dependent on reduced protease activity.