LncRNA-PCAT1 maintains characteristics of dermal papilla cells and promotes hair follicle regeneration by regulating miR-329/Wnt10b axis
LncRNA-PCAT1 maintains characteristics of dermal papilla cells and promotes hair follicle regeneration by regulating miR-329/Wnt10b axis
复制标题
LncRNA-PCAT1通过调节miR-329/Wnt10b轴维持真皮乳头细胞特性并促进毛囊再生
DOI：
10.1016/j.yexcr.2020.112031
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发表时间：
2020-09-01
影响因子：
3.7
通讯作者：
Yan, Yu-Yong
中科院分区：
文献类型：
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作者：
Lin, Bo-Jie;Lin, Guan-Yu;Yan, Yu-Yong
背景：毛囊再生障碍是脱发的主要原因，脱发是一种世界性的高发疾病。毛乳头细胞在毛囊再生的调控中起重要作用。方法：采用体外DP 3D培养和裸鼠体内DP球植入模型，研究DP细胞和毛囊再生的分子调控。qRT-PCR和Western blotting分别检测基因和蛋白表达。免疫荧光法检测Wnt 10 b、Ki-67和β-catenin的表达水平。荧光素酶法检测PCAT 1、miR-329和Wnt 10 b之间的关系。酶联免疫吸附法（ELISA）测定ALP活性。结果：在体外培养的3D毛乳头中，PCAT 1和Wnt 10 b表达上调，而miR-329表达下调。生物信息学分析和荧光素酶分析表明PCAT 1通过海绵状吸收miR-329促进Wnt 10 b的表达。PCAT 1的敲低通过靶向miR-329抑制DP细胞的增殖和活性以及ALP和其他DP标志物。PCAT 1的敲低调节miR-329/Wnt 10 b轴以减弱β-catenin表达和核转位以抑制Wnt/β-catenin信号传导。结论：PCAT 1通过靶向miR-329激活Wnt/beta-catenin信号通路，维持DP细胞的特性，从而促进毛囊再生。
Background: The failure of hair follicle regeneration is the major cause of alopecia, which is a highly prevalent disease worldwide. Dermal papilla (DP) cells play important role in the regulation of hair follicle regeneration. However, the molecular mechanism of how dermal papilla cells direct follicle regeneration is still to be elucidated.Methods: In vitro DP 3D culturing and in vivo nude mice DP sphere implanted models were used to examine the molecular regulation of DP cells and follicle regeneration. qRT-PCR and Western blotting were used to detect gene and protein expression, respectively. Immunofluorescence was used to detect the expression level of Wnt10b, Ki-67 and beta-catenin. Luciferase assay was used to examine the relationship among PCAT1, miR-329 and Wnt10b. ALP activity was measured by ELISA. H&E staining was used to measure follicle growth in skin tissues.Results: Up-regulation of PCAT1 and Wnt10b, however, down-regulation of miR-329 were found in the in vitro 3D dermal papilla. Bioinformatics analysis and luciferase assays demonstrated that PCAT1 promoted Wnt10b expression by sponging miR-329. Knockdown of PCAT1 suppressed the proliferation and activity, as well as ALP and other DP markers of DP cells by targeting miR-329. Knockdown of PCAT1 regulated miR-329/Wnt10b axis to attenuate beta-catenin expression and nucleus translocation to inhibit Wnt/beta-catenin signaling. Furthermore, knockdown of PCAT1 suppressed DP sphere induced follicle regeneration and hair growth in nude mice.Conclusion: PCAT1 maintains characteristics of DP cells by targeting miR-329 to activating Wnt/beta-catenin signaling pathway, thereby promoting hair follicle regeneration.