Necl2 regulates epidermal adhesion and wound repair
Necl2 regulates epidermal adhesion and wound repair
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DOI：
10.1242/dev.038232
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发表时间：
2009-10-15
期刊：
影响因子：
4.6
通讯作者：
Watt, Fiona M.
中科院分区：
文献类型：
--
作者：
Giangreco, Adam;Jensen, Kim B.;Watt, Fiona M.
在稳态条件下和组织修复期间，细胞粘附分子的差异表达调节干细胞定位、自我更新和谱系选择。我们发现，细胞间粘附蛋白nectin样分子2（Necl 2）在成年人和小鼠毛囊的隆突干细胞中高度表达。在培养的人角质形成细胞中Necl 2的过表达导致钙/钙调蛋白相关的Ser/Thr激酶（CASK）的上调，增加钙非依赖性细胞间粘附，以及抑制细胞运动和体外伤口愈合。虽然细胞增殖率降低，但终末分化不受影响。为了评估Necl 2在体内的作用，我们检查了Necl 2缺失小鼠的表皮，并开发了在小鼠表皮基底层中表达Necl 2的转基因小鼠。Necl 2过表达导致S期细胞减少，静止期细胞增加，在凸起处保留DNA标记。尽管转基因小鼠和基因敲除小鼠的表皮稳态均正常，但伤口愈合明显延迟。Necl 2过表达导致在愈合伤口的前沿增殖减少和CASK和E-钙粘蛋白水平增加，与其在培养中的作用一致。我们的研究结果表明，Necl 2参与调节表皮干细胞的静止和位置。
Differential expression of cell adhesion molecules regulates stem cell location, self-renewal and lineage selection under steady state conditions and during tissue repair. We show that the intercellular adhesion protein nectin-like molecule 2 (Necl2) is highly expressed in bulge stem cells of adult human and mouse hair follicles. Overexpression of Necl2 in cultured human keratinocytes led to upregulation of calcium/calmodulin-associated Ser/Thr kinase (CASK), increased calcium-independent intercellular adhesion, and inhibition of cell motility and in vitro wound healing. Although the rate of cell proliferation was reduced, terminal differentiation was unaffected. To assess the role of Necl2 in vivo, we examined the epidermis of Necl2-null mice and developed transgenic mice that expressed Necl2 in the basal layer of murine epidermis. Necl2 overexpression led to a reduction in S-phase cells and an increase in quiescent cells retaining DNA label in the bulge. Although epidermal homeostasis appeared normal in both transgenic and knockout mice, wound healing was markedly delayed. Necl2 overexpression resulted in reduced proliferation and increased levels of CASK and E-cadherin at the leading edge of healing wounds, consistent with its effects in culture. Our results demonstrate that Necl2 is involved in regulating epidermal stem cell quiescence and location.