LncRNA H19 Overexpression Activates Wnt Signaling to Maintain the Hair Follicle Regeneration Potential of Dermal Papilla Cells
LncRNA H19 Overexpression Activates Wnt Signaling to Maintain the Hair Follicle Regeneration Potential of Dermal Papilla Cells
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DOI：
10.3389/fgene.2020.00694
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发表时间：
2020-08-04
影响因子：
3.7
通讯作者：
Lin, Changmin
中科院分区：
文献类型：
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作者：
Zhu, Ningxia;Lin, En;Lin, Changmin
雄激素性脱发（AGA）是一种常见的脱发疾病，导致严重的社会交往异常和心理障碍。自体真皮乳头细胞移植是一种有前景的治疗方法。然而，真皮乳头细胞诱导毛囊发育的能力在细胞培养过程中丧失。长链非编码rna （Long non-coding RNAs, lncRNAs）是一类重要的参与多种生物学功能的基因，在疾病中异常表达，可能参与Wnt信号的调控，Wnt信号是维持真皮乳头细胞诱导毛囊能力的关键途径。lncRNA芯片检测真皮乳头细胞发现，与后期真皮乳头细胞相比，H19在早期真皮乳头细胞中高表达。在本研究中，我们构建了过表达H19的真皮乳头细胞来研究H19对毛囊诱导的作用。经编码H19的慢病毒感染的真皮乳头细胞在长时间培养后保持细胞形态，继续表现出多层聚集和诱导毛囊的能力。H19通过直接下调DKK1、Kremen2、sFRP2等Wnt抑制因子的表达，诱导miR-29a激活Wnt信号通路，从而在H19和miR-29a之间形成新的调控反馈回路，维持毛囊诱导电位，从而发挥这些作用。这些结果表明lncRNA H19通过激活Wnt通路维持真皮乳头细胞诱导毛囊的能力，可能成为治疗雄激素性脱发的靶点。
Androgenetic alopecia (AGA) is a common hair loss disorder resulting in seriously abnormal social interaction and psychological disorders. Transplantation with autologous dermal papilla cells represents a prospective therapy. However, the ability of dermal papilla cells to induce hair follicle development is lost upon cell culturing. Long non-coding RNAs (lncRNAs) are an important class of genes involved in various biological functions, are aberrantly expressed in disease and may play roles in the regulation of Wnt signaling, a critical pathway in maintaining the hair follicle-inducing capability of dermal papilla cells. Examination of dermal papilla cells by lncRNA microarray revealed that H19 was highly expressed in early passage dermal papilla cells compared with late-passage dermal papilla cells. In this study, we constructed H19-overexpressing dermal papilla cells to examine the role of H19 on hair follicle inductivity. Dermal papilla cells infected with lentivirus encoding H19 maintained their cell shape, and continued to display both multiple-layer aggregation and hair follicle-inducing ability upon prolonged culture. H19 exerted these effects through inducing miR-29a to activate Wnt signaling by directly downregulating the expression of Wnt suppressors, including DKK1, Kremen2, and sFRP2, thereby forming a novel regulatory feedback loop between H19 and miR-29a to maintain hair follicle- inducing potential. These results suggest that lncRNA H19 maintains the hair follicle-inducing ability of dermal papilla cells through activation of the Wnt pathway and could be a target for treatment of androgenetic alopecia.