Department of Burns and Plastic Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250000, Shandong, China.
Department of Mechanical Engineering, University of Maryland Baltimore County, Baltimore, MD, 21250, USA.
Arch Dermatol Res. 2018 Nov;310(9):737-750. doi: 10.1007/s00403-018-1863-3. Epub 2018 Sep 12.
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.
CD271 是神经生长因子 (NGF) 的受体，影响表皮干细胞 (eSCs) 的生物学特性，而表皮干细胞对于皮肤伤口闭合至关重要。另一种 NGF 受体 Tropomyosin-receptor kinase A (TrkA) 与 CD271 结合，与神经系统和皮肤角质形成细胞有关。然而，TrkA 与 CD271 在皮肤伤口闭合过程中在 eSCs 中的确切作用仍不清楚。本研究旨在揭示 TrkA 在 CD271 促进 eSCs 伤口愈合作用中的作用。我们通过慢病毒感染获得 CD271-vo（CD271 过表达）eSCs。使用 K252a 抑制 TrkA 表达。使用全层皮肤小鼠伤口闭合模型（直径 5mm）检测 CD271 过表达/TrkA 缺陷在伤口愈合过程中的作用。使用免疫组织化学和 Western blot 检测 eSCs 的生物学特性及其增殖和凋亡。Western blot 还检测了蛋白激酶 B (pAkt)/Akt、磷酸化细胞外信号调节激酶 (pERK)/ERK1/2 和 c-Jun N 末端激酶 (pJNK)/JNK 的表达。我们发现 CD271 的过表达促进了 eSCs 的生物学功能。有趣的是，在没有 TrkA 的情况下过表达 CD271 既不能促进 eSCs 的迁移和增殖，也不能促进小鼠模型中的伤口愈合。此外，我们观察到体外抑制 TrkA 后 pAkt/Akt 和 pERK/ERK1/2 的表达减少。我们的研究表明，TrkA 在 CD271 促进 eSCs 伤口愈合作用中的作用。
