The role of TrkA in the promoting wounding–healing effect of CD271 on epidermal stem cells
The role of TrkA in the promoting wounding–healing effect of CD271 on epidermal stem cells
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DOI：
10.1007/s00403-018-1863-3
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发表时间：
2018-09
影响因子：
3
通讯作者：
Min Zhang;Yuehou Zhang;Jun Ding;Xiaohong Li;C. Zang;S. Yin;Jiaxu Ma;Yibing Wang;Yong-qian Cao
中科院分区：
文献类型：
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作者：
Min Zhang;Yuehou Zhang;Jun Ding;Xiaohong Li;C. Zang;S. Yin;Jiaxu Ma;Yibing Wang;Yong-qian Cao
CD 271是神经生长因子（NGF）的受体，影响表皮干细胞（eSC）的生物学特性，而表皮干细胞对皮肤伤口闭合至关重要。原肌球蛋白受体激酶A（TrkA）是神经生长因子的另一种受体，与CD 271结合，参与神经系统和皮肤角质形成细胞。然而，在皮肤伤口闭合期间TrkA与CD 271组合在eSC中的确切作用仍不清楚。本研究旨在揭示TrkA在CD 271促进eSCs创伤愈合作用中的作用。我们通过慢病毒感染获得了CD 271-vo（CD 271的过表达）eSC。K252 a用于抑制TrkA表达。采用小鼠全层皮肤伤口闭合模型（直径5 mm）检测CD 271过表达/TrkA缺陷在伤口愈合过程中的能力。采用免疫组化和western blot检测eSCs的生物学特性及其增殖和凋亡情况。Western blot检测蛋白激酶B（pAkt）/Akt、磷酸化细胞外信号相关激酶（pERK）/ERK 1/2和c-Jun N-末端激酶（pJNK）/JNK的表达。我们发现CD 271的过表达促进了eSCs的生物学功能。有趣的是，在缺乏TrkA的情况下，CD 271的过表达既不促进eSC的迁移和增殖，也不促进小鼠模型中的伤口愈合。此外，我们还观察到TrkA抑制后pAkt/Akt和pERK/ERK 1/2的表达降低。我们的研究表明TrkA在CD 271对eSCs的促进伤口愈合作用中的作用。
CD271, a receptor of nerve growth factor (NGF), affects the biological properties of epidermal stem cells (eSCs) which are essential for skin wound closure. Tropomyosin-receptor kinase A (TrkA), another receptor of NGF, combined with CD271 has been involved with nervous system and skin keratinocytes. However, the exact role of TrkA combined with CD271 in eSCs during skin wound closure is still unclear. This study aimed to reveal the role of TrkA in the promoting wounding–healing effect of CD271 on eSCs. We obtained CD271-vo (over-expression of CD271) eSCs by lentiviral infection. K252a was used to inhibit TrkA expression. Full-thickness skin mouse wound closure model (5 mm in diameter) was used to detect the ability of CD271 over-expressed/TrkA-deficient during wound healing. The biological characteristics of eSCs and their proliferation and apoptosis were detected using immunohistochemistry and western blot. The expressions of protein kinase B (pAkt)/Akt, phosphorylated extracellular-signal-related kinase (pERK)/ERK1/2, and c-Jun N-terminal kinase (pJNK)/JNK were also detected by western blot. We found that over-expression of CD271 promoted the biological functions of eSCs. Interestingly, over-expression of CD271 in the absence of TrkA neither promoted eSCs’ migration and proliferation nor promoted wound healing in a mouse model. In addition, we observed the reduced expression of pAkt/Akt and pERK/ERK1/2 following TrkA inhibition in vitro. Our studies demonstrated that the role of TrkA in the promoting wounding–healing effect of CD271 on eSCs.