Fibronectin Expression Determines Skin Cell Motile Behavior
Fibronectin Expression Determines Skin Cell Motile Behavior
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DOI：
10.1038/jid.2011.297
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发表时间：
2012-02-01
影响因子：
6.5
通讯作者：
Jones, Jonathan C. R.
中科院分区：
文献类型：
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作者：
Hamill, Kevin J.;Hopkinson, Susan B.;Jones, Jonathan C. R.
小鼠角质形成细胞在体外无涂层表面上的迁移速度明显慢于人类。我们检验了这个假设，即这是细胞沉积的细胞外基质（ECM）差异的结果。为了支持这一观点，将人角质形成细胞镀在小鼠皮肤细胞的ECM上时，人角质形成细胞的运动性明显降低，而后者细胞镀在人角质形成细胞的ECM上时，迁移速度更快。小鼠和人角质形成细胞的ECM中含有相似水平的层粘连蛋白-332的α -3亚基。然而，小鼠皮肤细胞比人类细胞表达更多的纤维连接蛋白（FN）。为了评估FN是否为运动调节因子，我们使用小干扰RNA （siRNA）降低小鼠角质形成细胞中FN的表达。经处理的小鼠角质形成细胞的移动速度明显快于野生型小鼠皮肤细胞。此外，fn缺失的小鼠细胞ECM支持小鼠和人角质形成细胞的迁移增加。此外，当将人角质形成细胞以剂量依赖的方式镀在FN包被的底物上或人角质形成细胞ECM中补充FN时，其运动速度减慢。与这些发现一致的是，α 3整合素缺失的角质形成细胞的ECM也比野生型细胞迁移得更快，是FN缺陷的。我们的结果提供的证据表明，FN是一个刹车皮肤细胞迁移支持层粘连蛋白332-富基质。
Mouse keratinocytes migrate significantly slower than their human counterparts in vitro on uncoated surfaces. We tested the hypothesis that this is a consequence of differences in the extracellular matrix (ECM) that cells deposit. In support of this, human keratinocyte motility was markedly reduced when plated onto the ECM of mouse skin cells, whereas the latter cells migrated faster when plated onto human keratinocyte ECM. The ECM of mouse and human keratinocytes contained similar levels of the alpha 3 laminin subunit of laminin-332. However, mouse skin cells expressed significantly more fibronectin (FN) than human cells. To assess whether FN is a motility regulator, we used small interfering RNA (siRNA) to reduce the expression of FN in mouse keratinocytes. The treated mouse keratinocytes moved significantly more rapidly than wild-type mouse skin cells. Moreover, the FN-depleted mouse cell ECM supported increased migration of both mouse and human keratinocytes. Furthermore, the motility of human keratinocytes was slowed when plated onto FN-coated substrates or human keratinocyte ECM supplemented with FN in a dose-dependent manner. Consistent with these findings, the ECM of alpha 3 integrin-null keratinocytes, which also migrated faster than wild-type cells, was FN deficient. Our results provide evidence that FN is a brake to skin cell migration supported by laminin-332-rich matrices.