CAPN 7 promotes the migration and invasion of human endometrial stromal cell by regulating matrix metalloproteinase 2 activity.
CAPN 7 promotes the migration and invasion of human endometrial stromal cell by regulating matrix metalloproteinase 2 activity.
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CAPN 7通过调节基质金属蛋白酶2活性促进人子宫内膜基质细胞迁移和侵袭
DOI：
10.1186/1477-7827-11-64
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发表时间：
2013-07-15
期刊：
影响因子：
--
通讯作者：
Sun H
中科院分区：
文献类型：
--
作者：
Liu H;Jiang Y;Jin X;Zhu L;Shen X;Zhang Q;Wang B;Wang J;Hu Y;Yan G;Sun H
基质金属蛋白酶2 （MMP-2）已被报道在许多疾病中通过降解细胞外基质（ECM）调控细胞迁移和侵袭，如癌症和子宫内膜异位症。本研究发现，在诊断为子宫内膜异位症的女性中，钙活化中性蛋白酶7 （capn7）在异位子宫内膜和子宫内膜间质细胞中的表达明显上调。我们的研究旨在检测capn7对人子宫内膜基质细胞（hESC）迁移和侵袭的影响。方法采用western blotting和实时荧光定量PCR检测capn7在子宫内膜异位症患者和正常育龄妇女中的表达。采用刮伤愈合法和侵袭室法研究capn7在hESC迁移和侵袭中的作用。采用Western blotting、实时荧光定量PCR和酶谱法检测capn7对MMP-2表达和活性的影响。结果scapn7在子宫内膜异位症中明显上调，从而促进hESC的迁移和侵袭。capn7过表达导致MMP-2和组织金属蛋白酶抑制剂2 （TIMP-2）的表达增加；capn7基因敲低逆转了这些变化。capn7通过增加MMP-2与TIMP-2的比值来提高MMP-2的活性。我们还发现，OA-Hy（一种MMP-2抑制剂）可将capn7过表达对hESC迁移和侵袭的影响分别降低约50%和55%。此外，共免疫沉淀实验表明，capn7与激活蛋白2α (AP-2α)相互作用，AP-2α是MMP-2的重要转录因子。结论scapn7通过增加MMP-2 / TIMP-2的比例，提高MMP-2的活性，促进hESC的迁移和侵袭。
BackgroundMatrix metalloproteinase 2 (MMP-2) has been reported to be an important regulator of cell migration and invasion through degradation of the extracellular matrix (ECM) in many diseases, such as cancer and endometriosis. Here, we found calcium-activated neutral protease 7 (CAPN 7) expression was markedly upregulated in the eutopic endometrium and endometrial stromal cells of women diagnosed with endometriosis. Our studies were carried out to detect the effects of CAPN 7 on human endometrial stromal cell (hESC) migration and invasion.MethodsWestern blotting and quantitative real-time PCR were used to detect the expression of CAPN 7 in endometriosis patients and normal fertile women. Scratch-wound-healing and invasion chamber assay were used to investigate the role of CAPN 7 in hESC migration and invasion. Western blotting, quantitative real-time PCR and zymography were carried out to detect the effect of CAPN 7 on the expressions and activity of MMP-2.ResultsCAPN 7 was markedly up-regulated in endometriosis, thereby promoting the migration and invasion of hESC. CAPN 7 overexpression led to increased expression of MMP-2 and tissue inhibitor of metalloproteinases 2 (TIMP-2); CAPN 7 knockdown reversed these changes. CAPN 7 increased MMP-2 activity by increasing the ratio of MMP-2 to TIMP-2. We also found that OA-Hy (an MMP-2 inhibitor) decreased the effects of CAPN 7 overexpression on hESC migration and invasion by approximately 50% and 55%, respectively. Additionally, a coimmunoprecipitation assay demonstrated that CAPN 7 interacted with activator protein 2α (AP-2α): an important transcription factor of MMP-2.ConclusionsCAPN 7 promotes hESC migration and invasion by increasing the activity of MMP-2 via an increased ratio of MMP-2 to TIMP-2.
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影响因子：
6.1
作者：
Collette, T.;Maheux, R.;Akoum, A.
通讯作者：
Akoum, A.
孤儿核受体Nur77调节人子宫内膜基质细胞中蜕膜催乳素的表达
DOI：
10.1016/j.bbrc.2010.12.027
发表时间：
2011-01-14
影响因子：
3.1
作者：
Jiang, Yue;Hu, Yali;Sun, Haixiang
通讯作者：
Sun, Haixiang
影响因子：
4.8
作者：
Cortesio, Christa L.;Boateng, Lindsy R.;Huttenlocher, Anna
通讯作者：
Huttenlocher, Anna
影响因子：
4.4
作者：
Jang, Hyo Sang;Lal, Sangeet;Greenwood, Jeffrey A.
通讯作者：
Greenwood, Jeffrey A.
DOI：
10.2147/ijwh.s5633
发表时间：
2011
期刊：
International journal of women's health
影响因子：
--
作者：
Schindler AE
通讯作者：
Schindler AE