IL-36α Promoted Wound Induced Hair Follicle Neogenesis via Hair Follicle Stem/Progenitor Cell Proliferation
IL-36α Promoted Wound Induced Hair Follicle Neogenesis via Hair Follicle Stem/Progenitor Cell Proliferation
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DOI：
10.3389/fcell.2020.00627
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发表时间：
2020-09-02
影响因子：
5.5
通讯作者：
Xu, Xuegang
中科院分区：
文献类型：
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作者：
Gong, Lin;Xiao, Jian;Xu, Xuegang
背景资料：创伤诱导的毛囊新生（WIHN）是当创伤面积足够大时在瘢痕中心发生的毛发新生现象。在伤口边缘，新生毛囊通过无毛圆形区域与先前存在的毛囊分开。WIHN的这项研究提供了一个独特的模型，用于开发脱发的治疗方法，并破译成年哺乳动物器官发生的机制。方法：通过切除1.5 × 1.5 cm（2）的全层背部皮肤，使小鼠皮肤受伤。在创伤后第15天，使用iTRAQ技术筛选WIHN小鼠模型中内外瘢痕区域之间差异表达的蛋白质，以鉴定WIHN的调节剂。由于白细胞介素-36 α（IL-36 α）在新生毛囊生长区的过度表达，本研究探讨了IL-36 α过度表达对WIHN的调节作用。采用流式细胞仪检测毛囊干/祖细胞数量，qPCR和western blotting检测毛囊干/祖细胞标志物（Lgr 5、Lgr 6、Lrig 1、K15和CD 34）以及Wnt/beta-catenin和IL-6/STAT 3通路中间体的表达。将重组鼠IL-36 α（mrIL-36 α）掺入鼠皮肤伤口中导致再生毛囊数量更多（p< 0.005）和愈合速度更快。毛囊干/祖细胞标记物的表达在mrIL-36 α注射部位上调（p< 0.05）。结论：IL-36 α在新生毛囊生长区表达上调，并能促进创面上皮化和WIHN。
Background: Wound-induced hair follicle neogenesis (WIHN) is a phenomenon of hair neogenesis that occurs at the center of a scar when the wound area is sufficiently large. Neogenic hair follicles are separated from the pre-existing follicles at the wound edge by a hairless circular region. This WIHN study provides a unique model for developing treatments for hair loss and deciphering the mechanisms underlying organogenesis in adult mammals.Methods: The skin of a mouse was wounded by excising a 1.5 x 1.5 cm(2) square of full-thickness dorsal skin. iTRAQ technology was used to screen proteins differentially expressed between the inner and outer scar areas in a mouse model of WIHN, on post-wounding day 15, to identify the regulators of WIHN. Owing to the overexpression of interleukin-36 alpha (IL-36 alpha) in thede novohair follicle growth area, the regulating effect of IL-36 alpha overexpression in WIHN was investigated. Hair follicle stem/progenitor cells were counted by flow cytometry while the expression of hair follicle stem/progenitor cell markers (Lgr5, Lgr6, Lrig1, K15, andCD34) and that of Wnt/beta-catenin and IL-6/STAT3 pathway intermediaries was detected by qPCR and western blotting.Results: We found that wounding induced IL-36 alpha expression. Incorporation of recombinant murine IL-36 alpha (mrIL-36 alpha) into murine skin wounds resulted in a greater number of regenerated hair follicles (p< 0.005) and a faster healing rate. The expression of hair follicle stem/progenitor cell markers was upregulated in the mrIL-36 alpha-injected site (p< 0.05). Additionally, mrIL-36 alpha upregulated the IL-6/STAT3 pathway : intermediaries.Conclusion: IL-36 alpha is upregulated inde novohair follicle growth areas and can promote wound epithelialization and WIHN.