Evidence for a cooperative role of gelatinase A and membrane type-1 matrix metalloproteinase during Xenopus laevis development
Evidence for a cooperative role of gelatinase A and membrane type-1 matrix metalloproteinase during Xenopus laevis development
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DOI：
10.1016/j.mod.2006.09.001
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发表时间：
2007-01-01
影响因子：
2.6
通讯作者：
Shi, Yun-Bo
中科院分区：
文献类型：
--
作者：
Hasebe, Takashi;Hartman, Rebecca;Shi, Yun-Bo
基质金属蛋白酶（MMP）是细胞外或膜结合蛋白酶的大家族。它们切割细胞外基质（ECM）蛋白的能力暗示了在ECM重塑中的作用，从而影响发育期间和发病机制中的细胞命运和行为。我们以前已经表明，膜型1（MT-1）-MMP的时间和空间共表达的MMP明胶酶A（GelA）在所有类型的肠和尾巴，其中GelA是表达在非洲爪蟾变态，这表明这些MMPs在发展中的合作作用。在这里，我们表明，非洲爪蟾GelA和MT 1-MMP相互作用，在体内和过度表达MT 1-MMP和GelA一起在非洲爪蟾胚胎中导致前GelA的激活。我们进一步表明，这两种MMP在非洲爪蟾胚胎发生过程中表达，虽然MT 1-MMP基因的表达早于GelA基因。为了研究胚胎基质金属蛋白酶是否在发育中发挥作用，我们研究了这些基质金属蛋白酶的早熟表达是否会改变发育。我们的研究结果表明，这两种基质金属蛋白酶的过度表达导致发育异常和胚胎死亡的机制，需要的基质金属蛋白酶的催化活性。更重要的是，我们表明，野生型MT 1-MMP和GelA的共表达导致对胚胎发育的协同作用，这种协同作用被废除时，任何MMP的催化活性是通过在催化结构域的点突变消除。因此，我们的研究支持这些MMPs在胚胎发育中的合作作用，可能是通过MT 1-MMP激活前GelA。(c)2006爱思唯尔爱尔兰有限公司保留所有权利。
Matrix metalloproteinases (MMPs) are a large family of extracellular or membrane-bound proteases. Their ability to cleave extracellular matrix (ECM) proteins has implicated a role in ECM remodeling to affect cell fate and behavior during development and in pathogenesis. We have shown previously that membrane-type 1 (MT-1)-MMP is coexpressed temporally and spatially with the MMP gelatinase A (GelA) in all cell types of the intestine and tail where GelA is expressed during Xenopus laevis metamorphosis, suggesting a cooperative role of these MMPs in development. Here, we show that Xenopus GelA and MT1-MMP interact with each other in vivo and that overexpression of MT1-MMP and GelA together in Xenopus embryos leads to the activation of pro-GelA. We further show that both MMPs are expressed during Xenopus embryogenesis, although MT1-MMP gene is expressed earlier than the GelA gene. To investigate whether the embryonic MMPs play a role in development, we have studied whether precocious expression of these MMPs alters development. Our results show that overexpression of both MMPs causes developmental abnormalities and embryonic death by a mechanism that requires the catalytic activity of the MMPs. More importantly, we show that coexpression of wild type MT1-MMP and GelA leads to a cooperative effect on embryonic development and that this cooperative effect is abolished when the catalytic activity of either MMP is eliminated through a point mutation in the catalytic domain. Thus, our studies support a cooperative role of these MMPs in embryonic development, likely through the activation of pro-GelA by MT1-MMP. (c) 2006 Elsevier Ireland Ltd. All rights reserved.