title: Hair follicle stem cell proliferation, Akt and Wnt signaling activation in TPA-induced hair regeneration.
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.
authors.affiliation: Department of Cell Biology, College of Basic Medical Science, Third Military Medical University, Chongqing, 400038, China.|Department of Dermatology, Wuhan General Hospital of the Chinese People's Liberation Army, Wuhan, 430070, China.
authors.forename: Weiming
authors.initials: W
authors.lastname: Qiu
authors.affiliation: "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.
authors.forename: Mingxing
authors.initials: M
authors.lastname: Lei
authors.affiliation: Department of Dermatology, Wuhan General Hospital of the Chinese People's Liberation Army, Wuhan, 430070, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Cell Biology, College of Basic Medical Science, Third Military Medical University, Chongqing, 400038, China.
authors.forename: Xiufeng
authors.initials: X
authors.lastname: Bai
authors.affiliation: "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.
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Lai
authors.affiliation: Department of Cell Biology, College of Basic Medical Science, Third Military Medical University, Chongqing, 400038, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Cell Biology, College of Basic Medical Science, Third Military Medical University, Chongqing, 400038, China.
authors.forename: Tian
authors.initials: T
authors.lastname: Yang
authors.affiliation: Department of Cell Biology, College of Basic Medical Science, Third Military Medical University, Chongqing, 400038, China. lianxiaohua12@163.com.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Lian
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D006197:Hair / Q000187:drug effects* / Q000254:growth & development* / Q000378:metabolism; D018859:Hair Follicle / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012038:Regeneration / Q000187:drug effects*; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D051153:Wnt Proteins / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000187:drug effects*
chemical_list: D051153:Wnt Proteins; D051057:Proto-Oncogene Proteins c-akt; D013755:Tetradecanoylphorbol Acetate
keywords: DKK1; Hair follicle stem cell; Hair regeneration; TPA; Wnt/β-catenin signaling