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Hair follicle stem cell proliferation, Akt and Wnt signaling activation in TPA-induced hair regeneration

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Abstract

Regeneration of hair follicles relies on activation of hair follicle stem cells during telogen to anagen transition process in hair cycle. This process is rigorously controlled by intrinsic and environmental factors. 12-o-tetradecanoylphorbol-13-acetate (TPA), a tumor promoter, accelerates reentry of hair follicles into anagen phase. However, it is unclear that how TPA promotes the hair regeneration. In the present study, we topically applied TPA onto the dorsal skin of 2-month-old C57BL/6 female mice to examine the activity of hair follicle stem cells and alteration of signaling pathways during hair regeneration. We found that refractory telogen hair follicles entered anagen prematurely after TPA treatment, with the enhanced proliferation of CD34-positive hair follicle stem cells. Meanwhile, we observed Akt signaling was activated in epidermis, hair infundibulum, bulge and hair bulb, and Wnt signaling was also activated after hair follicle stem cells proliferation. Importantly, after overexpression of DKK1, a specific Wnt signaling inhibitor, the accelerated reentry of hair follicles into anagen induced by TPA was abolished. Our data indicated that TPA-induced hair follicle regeneration is associated with activation of Akt and Wnt/β-catenin signaling.

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Abbreviations

H&E:

Hematoxylin and eosin staining

ORS:

Outer root sheath

RT-PCR:

Reverse transcription-polymerase chain reaction

TPA:

12-o-Tetradecanoylphorbol-13-acetate

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Acknowledgements

This study was supported by the National Nature Science Foundation of China (30972645 and 81602782), and Natural Science Foundation of Hubei Province (2016CFB348). Mingxing Lei is supported by Project funded by China Postdoctoral Science Foundation (2016M590866), Fundamental Research Funds for the Central Universities (106112015CDJRC231206), Special Funding for Postdoctoral Research Projects in Chongqing (Xm2015093), and a fellowship from the China Scholarship Council (2011605042).

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Authors and Affiliations

  1. Department of Cell Biology, College of Basic Medical Science, Third Military Medical University, Chongqing, 400038, China

    Weiming Qiu, Xiufeng Bai, Yu Yu, Tian Yang & Xiaohua Lian

  2. Department of Dermatology, Wuhan General Hospital of the Chinese People’s Liberation Army, Wuhan, 430070, China

    Weiming Qiu & Ling Zhou

  3. “111” Project Laboratory of Biomechanics and Tissue Repair and Key Laboratory of Biorheological Science and Technology of Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, 400044, China

    Mingxing Lei & Xiangdong Lai

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  1. Weiming Qiu
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Correspondence to Xiaohua Lian.

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Qiu, W., Lei, M., Zhou, L. et al. Hair follicle stem cell proliferation, Akt and Wnt signaling activation in TPA-induced hair regeneration. Histochem Cell Biol 147, 749–758 (2017). https://doi.org/10.1007/s00418-017-1540-1

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