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.

雄激素性脱发（AGA）是一种常见的脱发疾病，会导致严重的社交互动和心理疾病。自体真皮乳头细胞移植代表了一种前瞻性疗法。但是，真皮乳头细胞诱导毛囊发育的能力在细胞培养后丧失。长非编码RNA（lncRNA）是涉及各种生物学功能的重要基因类别，在疾病中异常表达，并且可能在Wnt信号的调控中发挥作用，Wnt信号是维持皮肤乳头毛囊诱导能力的关键途径细胞。通过lncRNA芯片对真皮乳头细胞的检查显示，与传代晚期真皮乳头细胞相比，H19在早期传代真皮乳头细胞中高表达。在这个研究中，我们构建了H19过表达的真皮乳头细胞，以检查H19对毛囊诱导性的作用。感染编码H19的慢病毒的皮肤乳头细胞保持其细胞形状，并在长时间培养后继续表现出多层聚集和毛囊诱导能力。H19通过直接下调Wnt抑制因子（包括DKK1，Kremen2和sFRP2）的表达来诱导miR-29a激活Wnt信号传导，从而发挥了这些作用，从而在H19和miR-29a之间形成了新型的调节反馈环，从而保持了毛囊诱导的潜力。 。这些结果表明，lncRNA H19通过激活Wnt途径维持真皮乳头细胞的毛囊诱导能力，并可能成为雄激素性脱发的治疗靶标。