Downregulation of CD9 in keratinocyte contributes to cell migration via upregulation of matrix metalloproteinase-9.
Downregulation of CD9 in keratinocyte contributes to cell migration via upregulation of matrix metalloproteinase-9.
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DOI：
10.1371/journal.pone.0077806
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Huang YS
中科院分区：
文献类型：
--
作者：
Jiang XP;Zhang DX;Teng M;Zhang Q;Zhang JP;Huang YS
Tetraspanin CD9参与多种细胞和生理过程，包括细胞迁移。在我们之前的研究中，我们发现CD9缺失的小鼠伤口修复延迟，这表明CD9对皮肤伤口愈合至关重要。然而，许多细胞类型，包括免疫细胞、内皮细胞、角质形成细胞和成纤维细胞，在创伤修复过程中经历了显著的基因表达和表型变化，导致细胞增殖、迁移和分化，CD9是否直接调控角质形成细胞的迁移尚不清楚。在这项研究中，我们发现CD9在体内和体外创伤修复过程中迁移的角质形成细胞中的表达下调。构建CD9沉默或过表达重组腺病毒载体，感染HaCaT细胞。通过细胞划痕实验和细胞迁移实验，我们还证明了CD9的下调促进了角质形成细胞在体外的迁移，而CD9的过表达抑制了细胞的迁移。此外，CD9还反向调节角质形成细胞中基质金属蛋白酶-9的活性和表达，参与CD9调控的角质形成细胞迁移。重要的是，CD9沉默激活的JNK信号伴随着基质金属蛋白酶-9活性和表达的上调。巧合的是，我们发现JNK途径抑制剂SP600125降低了CD9沉默的HaCaT细胞的活性和基质金属蛋白酶-9的表达。因此，我们的结果表明，CD9在体内和体外迁移的角质形成细胞中表达下调，而低水平的CD9在体外促进角质形成细胞的迁移，其中通过JNK途径对基质金属蛋白酶-9的调节起着重要作用。
Tetraspanin CD9 has been implicated in various cellular and physiological processes, including cell migration. In our previous study, we found that wound repair is delayed in CD9-null mice, suggesting that CD9 is critical for cutaneous wound healing. However, many cell types, including immune cells, endothelial cells, keratinocytes and fibroblasts undergo marked changes in gene expression and phenotype, leading to cell proliferation, migration and differentiation during wound repair, whether CD9 regulates kerationcytes migration directly remains unclear. In this study, we showed that the expression of CD9 was downregulated in migrating keratinocytes during wound repair in vivo and in vitro. Recombinant adenovirus vector for CD9 silencing or overexpressing was constructed and used to infect HaCaT cells. Using cell scratch wound assay and cell migration assay, we have also demonstrated that downregulation of CD9 promoted keratinocyte migration in vitro, whereas CD9 overexpression inhibited cell migration. Moreover, CD9 inversely regulated the activity and expression of MMP-9 in keratinocytes, which was involved in CD9-regulated keratinocyte migration. Importantly, CD9 silencing-activated JNK signaling was accompanied by the upregulation of MMP-9 activity and expression. Coincidentally, we found that SP600125, a JNK pathway inhibitor, decreased the activity and expression of MMP-9 of CD9-silenced HaCaT cells. Thus, our results suggest that CD9 is downregulated in migrating keratinocytes in vivo and in vitro, and a low level of CD9 promotes keratinocyte migration in vitro, in which the regulation of MMP-9 through the JNK pathway plays an important role.
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影响因子：
8.7
作者：
Klein-Soyer, C;Azorsa, DO;Lanza, F
通讯作者：
Lanza, F
影响因子：
8
作者：
Ekekezie, II;Thibeault, DW;Truog, WE
通讯作者：
Truog, WE
影响因子：
4.8
作者：
Gutierrez-Fernandez, Ana;Inada, Masaki;Puente, Xose S.
通讯作者：
Puente, Xose S.
影响因子：
6.5
作者：
García-López, MA;Barreiro, O;Peñas, PF
通讯作者：
Peñas, PF
DOI：
10.1016/j.biocel.2012.01.020
发表时间：
2012-05-01
影响因子：
4
作者：
Bassani, Silvia;Cingolani, Lorenzo A.
通讯作者：
Cingolani, Lorenzo A.