Human amniotic epithelial stem cells promote wound healing by facilitating migration and proliferation of keratinocytes via ERK, JNK and AKT signaling pathways
Human amniotic epithelial stem cells promote wound healing by facilitating migration and proliferation of keratinocytes via ERK, JNK and AKT signaling pathways
复制标题
DOI：
10.1007/s00441-016-2366-1
复制
发表时间：
2016-07-01
影响因子：
3.6
通讯作者：
Hu, Da-Hai
中科院分区：
文献类型：
--
作者：
Zhao, Bin;Liu, Jia-Qi;Hu, Da-Hai
伤口愈合是一个高度协调的生理过程，包括细胞和生物化学事件的复杂相互作用。人羊膜上皮干细胞（HAESC）已被证明是一个有吸引力的资源，伤口愈合，因为他们是原始的干细胞。然而，表皮干细胞对角质形成细胞迁移或增殖的确切影响及其潜在机制尚未完全了解。我们已经发现，HAESC加速角质形成细胞的迁移并诱导磷酸化ERK、磷酸化JNK和磷酸化AKT活性的显著增加，通过其特异性抑制剂对其的阻断显著抑制了HAESC条件培养基（CM）诱导的迁移。此外，角质形成细胞与HAESC的共培养上调细胞增殖蛋白Cyclin D1、Cyclin D3和Mdm 2的表达水平。体内动物实验已经显示，HAESC-CM改善伤口愈合，而用ERK、JNK和AKT抑制剂阻断显著损害伤口愈合。总之，这些结果首次揭示了HAESC通过ERK、JNK和AKT信号通路促进角质形成细胞的迁移和增殖来促进伤口愈合，并且可能是皮肤伤口愈合的潜在疗法。
Wound healing is a highly orchestrated physiological process consisting in a complex interaction of cellular and biochemical events. Human amniotic epithelial stem cells (HAESCs) have been shown to be an attractive resource for wound healing because they are primitive stem cells. However, the exact effects of amnion-derived stem cells on the migration or proliferation of keratinocytes and their potential mechanism are not fully understood. We have found that HAESCs accelerate the migration of keratinocytes and induce a remarkable increase in the activity of phospho-ERK, phospho-JNK, and phospho-AKT, the blockade of which by their specific inhibitors significantly inhibits migration induced by HAESC-conditioned medium (CM). Furthermore, the co-culture of keratinocytes with HAESCs up-regulates the expression levels of cell proliferation proteins Cyclin D1, Cyclin D3 and Mdm2. In vivo animal experiments have shown that HAESC-CM improves wound healing, whereas blockade with ERK, JNK and AKT inhibitors significantly impairs wound healing. Taken together, these results reveal, for the first time, that HAESCs promote wound healing by facilitating the migration and proliferation of keratinocytes via ERK, JNK and AKT signaling pathways and might be a potential therapy in skin wound healing.