Elimination of epiplakin by gene targeting results in acceleration of keratinocyte migration in mice
Elimination of epiplakin by gene targeting results in acceleration of keratinocyte migration in mice
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DOI：
10.1128/mcb.26.2.548-558.2006
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发表时间：
2006-01-01
影响因子：
5.3
通讯作者：
Fujiwara, S
中科院分区：
文献类型：
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作者：
Goto, M;Sumiyoshi, H;Fujiwara, S
Epiplakin （EPPK）最初被认为是一种人表皮自身抗原。为了确定epiplakin的功能，我们产生了epiplakin“敲除”小鼠。这些小鼠发育正常，表皮和毛发明显正常。免疫染色电镜显示野生型小鼠角蛋白丝附近存在EPPK，提示epiplakin可能与角蛋白相关。EPPK-/-小鼠完整表皮角质形成细胞中角蛋白束的外观和定位与野生型小鼠相似。EPPK-/-小鼠背部伤口愈合速度快于野生型和杂合型小鼠。即使在丝裂霉素C的存在下，基因敲除小鼠皮肤外植体的角质形成细胞的生长也比野生型小鼠的外植体的生长增强，这表明角质形成细胞生长的差异可能是由于角质形成细胞迁移速度的差异。在野生型小鼠的伤口边缘，EPPK与角蛋白6一起在增殖的角质形成细胞中表达。在EPPK-/-小鼠中，没有观察到类似的增殖角化细胞，但迁移的角化细胞弱表达角蛋白6。在野生小鼠外植体培养的部分角质形成细胞中，EPPK与角蛋白6共表达。我们认为EPPK可能与角蛋白6有功能上的联系。
Epiplakin (EPPK) was originally identified as a human epidermal autoantigen. To identify the function of epiplakin, we generated epiplakin "knockout" mice. These mice developed normally, with apparently normal epidermis and hair. Electron microscopy after immunostaining revealed the presence of EPPK adjacent to keratin filaments in wild-type mice, suggesting that epiplakin might associate with keratin. The appearance and localization of keratin bundles in intact epidermal keratinocytes of EPPK-/- mice were similar to those in wild-type mice. Wounds on the backs of EPPK-/- mice closed more rapidly than those on the backs of wild-type and heterozygous mice. The outgrowth of keratinocytes from skin explants from knockout mice was enhanced compared to outgrowth from explants from wild-type mice, even in the presence of mitomycin C, suggesting that the difference in keratinocyte outgrowth might be due to a difference in the speed of migration of keratinocytes. At wound edges in wild-type mice, EPPK was expressed in proliferating keratinocytes in conjunction with keratin 6. In EPPK-/- mice, no similar proliferating keratinocytes were observed, but migrating keratinocytes weakly expressed keratin 6. EPPK was coexpressed with keratin 6 in some keratinocytes in explant cultures from wild mice. We propose that EPPK might be linked functionally with keratin 6.