Soluble membrane-type 3 matrix metalloprioteinase causes changes in gene expression and increased gelatinase activity during Xenopus laevis development.

Soluble membrane-type 3 matrix metalloprioteinase causes changes in gene expression and increased gelatinase activity during Xenopus laevis development.
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在非洲爪蟾发育过程中,可溶性膜 3 型基质金属蛋白酶会导致基因表达发生变化并增加明胶酶活性。

DOI:
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发表时间:
2007
影响因子:
0.7
通讯作者:
S. Damjanovski
S. Damjanovski
中科院分区:
生物学4区
文献类型:
--
作者:
L. Walsh;Colin A. Cooper;S. Damjanovski

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基质金属蛋白酶(MMPs)是一类切割和重塑细胞外基质(ECM)的内肽酶家族。膜型3型基质金属蛋白酶(MT3-MMPs)是一种膜锚定的基质金属蛋白酶,最近发现它在蛋白质降解后以可溶的形式从细胞表面“脱落”出来。脱落型MT-MMPs在体外可以激活明胶酶-A,并与许多癌症的转移潜能直接相关。在这里,我们研究了非洲爪哇发育过程中全长、拴系型和脱落型(可溶)MT3-MMP异位表达的影响。注射编码全长MT3-MMPmRNA导致原肠形成延迟和随后的缺陷。表型严重程度和胚胎死亡频率呈剂量依赖关系。注射可溶性形式的mRNA也可以观察到剂量依赖性的缺陷,但死亡的表型和频率更高。对注射的胚胎进行的组织学分析显示,神经管和体节等轴向结构的组织存在缺陷。半定量RT-PCR检测显示,注射全长MT3-MMPmRNA的胚胎组织特异性基因enddermin、Chordin和肌肉肌动蛋白的表达水平没有显著变化。相比之下,注射可溶性MT3-MMPs的胚胎表现出这些相同标记基因的表达减少。此外,虽然全长的MT3-MMP不能改变明胶酶的活性,但注射可溶性形式后明胶酶活性增加了50%,这表明这两种形式的蛋白在胚胎发育过程中可能发挥着不同的作用。
Matrix metalloproteinases (MMPs) are a family of endopeptidases that cleave and remodel the extracellular matrix (ECM). Membrane-type 3 MMP (MT3-MMP) is a membrane-anchored MMP, which has recently been shown to 'shed' from the cell surface in a soluble form upon proteolytic cleavage. Shed MT-MMPs can activate gelatinase-A in vitro and have been directly linked to the metastatic potential of many cancers. Here we examined the effect of ectopic expression of full-length tethered and shed (soluble) forms of MT3-MMP during Xenopus laevis development. Injection of mRNA coding for full-length tethered MT3-MMP resulted in the delayed onset of gastrulation and subsequent defects. Phenotype severity and the frequency of embryo death were dose-dependent. Dose-dependent defects were also observed with the injection of mRNA of the soluble form, but the phenotypes and frequencies of death were greater. Histological analysis of injected embryos demonstrated defects in the organization of axial structures, such as the neural tube and somites. Embryos injected with full-length MT3-MMP mRNA showed no significant changes in expression levels of the tissue specific genes endodermin, chordin and muscle actin when examined by semi-quantitative RT-PCR. In contrast, embryos injected with the soluble form of MT3-MMP exhibited decreased expression of these same marker genes. In addition, while full-length tethered MT3-MMP failed to alter gelatinase activity, a 50% increase was measured in response to injection of the soluble form, suggesting that the two forms of this protein could play distinct roles during embryogenesis.
两栖动物胚胎发生过程中组蛋白脱乙酰酶的多个阶段依赖性作用:对细胞外基质重塑参与的影响。
DOI: --
发表时间: 2000
期刊: The International journal of developmental biology
影响因子: --
作者:
Damjanovski,S;Sachs,LM;Shi,YB
通讯作者: Shi,YB
EGF 和 TGF α 通过诱导基质降解金属蛋白酶影响体外肺发育。
DOI: --
发表时间: 1991
期刊: The International journal of developmental biology
影响因子: --
作者:
Ganser,GL;Stricklin,GP;Matrisian,LM
通讯作者: Matrisian,LM
DOI: 10.1007/s00586-002-0454-2
发表时间: 2003-02-01
影响因子: 2.8
作者:
Shen, B;Melrose, J;Taylor, TKF
通讯作者: Taylor, TKF