PlncRNA-1 stimulates hair follicle stem cell differentiation in wound healing via the EZH2/ZEB1/MAPK1 axis

waynakyo

Experienced Member
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Abstract​

Background: Hair follicles have been reported to contribute to epidermal healing, with differentiation of hair follicle stem cells (HFSCs) aiding in wound re-epithelialization. This study is aimed to delineate the molecular mechanistic actions by which prostate cancer-upregulated long noncoding RNA 1 (PlncRNA-1) accelerates the proliferation and differentiation of HFSCs in wound healing.
Methods: HFSCs were obtained from the scalps of five volunteers, in which the expression of PlncRNA-1 and downstream regulatory genes was identified. Effects of PlncRNA-1 overexpression and ZEB1 knockdown on the proliferation and differentiation of HFSCs were examined. A wound mouse model was further established for in vivo experiments to substantiate in vitro findings.
Results: PlncRNA-1 is highly expressed in HFSCs and accelerates the proliferation and differentiation of HFSCs. PlncRNA-1 recruits EZH2 to ZEB1 promoter region and augments the H3K27me3 methylation, thereby downregulating the expression of ZEB1. Without such suppression, ZEB1 could repress MAPK1 expression and restrict HFSC proliferation and differentiation. Further, PlncRNA-1 overexpression accelerates wound healing and epidermal regeneration in vivo.
Conclusions: PlncRNA-1 inhibits ZEB1 and activates MAPK1 signaling through upregulating EZH2, thereby enhancing the proliferation and differentiation of HFSCs and wound healing.
Keywords: Enhancer of zeste homolog 2; Epidermal regeneration; H3K27me3; Hair follicle stem cells; Mitogen activated protein kinase 1; PlncRNA-1; Proliferation and differentiation; Wound healing; ZEB1.
 
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