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The role of TrkA in the promoting wounding–healing effect of CD271 on epidermal stem cells

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Abstract

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.

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Abbreviations

Egfr:

Epidermal growth receptor

eSCs:

Epidermal stem cells

GAPDH:

Glyceraldehydes-3-phosphate dehydrogenase

NGF:

Nerve growth factor

PI:

Propidium iodide

TAC:

Transit amplifying cells

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Acknowledgements

Yibing Wang and Xiaohong Li conceived and designed the experiments; Min Zhang performed the experiments; Yuehou Zhang and Jiaxu Ma contributed reagents, materials, and analysis tools; Jun Ding, Siyuan Yin and Yongqian Cao analyzed the data; Xiaohong Li and Min Zhang wrote the paper; Xiaohong Li, Faming Tian, Yuan Li, and Jun Ding review the paper and references.

Funding

This study was funded by the National Natural Science Foundation of China (No. 81571911 and 81772092), and Science and Technology Development Program of Shandong Province (No. 2016GSF201080).

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Authors and Affiliations

  1. Department of Burns and Plastic Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250000, Shandong, China

    Min Zhang, Yuehou Zhang, Chengyu Zang, Siyuan Yin, Jiaxu Ma, Yibing Wang & Yongqian Cao

  2. Department of Mechanical Engineering, University of Maryland Baltimore County, Baltimore, MD, 21250, USA

    Jun Ding

  3. Health Management Center, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250000, Shandong, China

    Xiaohong Li

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  1. Min Zhang
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Correspondence to Yibing Wang or Yongqian Cao.

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Ethical approval

All involved animals were performed according to the National Institutes of Health (NIH) Guide. Under pentobarbital sodium anesthesia, all surgeries were performed. Followed by the Committee on the Ethics of Shandong University, the experiments were approved.

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Zhang, M., Zhang, Y., Ding, J. et al. The role of TrkA in the promoting wounding–healing effect of CD271 on epidermal stem cells. Arch Dermatol Res 310, 737–750 (2018). https://doi.org/10.1007/s00403-018-1863-3

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