MiR-195-5p Regulates Hair Follicle Inductivity of Dermal Papilla Cells by Suppressing Wnt/β-Catenin Activation.

Ningxia Zhu,Bozhi Cai,Keng Huang,Changmin Lin,Yu Li,En Lin,Huan Zhang,Yanping Yuan,Yanming Xu,Yang Zeng,Haihong Li,Yang Liu

doi:10.1155/2018/4924356

Abstract

Dermal papilla (DP) cells play a vital role in hair follicle (HF) development and postnatal hair cycling. However, the abilities are lost on further culture. Recent studies have demonstrated significant influences of posttranscriptional regulation by microRNA (miRNA) on HF development. The current study aims to investigate how miRNAs regulate Wnt/β-catenin to control HF inductivity of DP cells by performing microarray analysis in early- and late-passage DP cells and transfecting with miRNAs inhibitor or mimic. Results showed early-passage DP cells strongly expressed miRNAs related to inhibition of noncanonical Wnt pathways. In late-passage DP cells, miRNAs capable of inhibiting the canonical Wnt/β-catenin pathway were upregulated, in addition to the miRNAs targeting the noncanonical Wnt pathway. Moreover, we verified that β-catenin expression was downregulated by miR-195-5p overexpression in dose manner. Meanwhile LRP6 expression was downregulated in both protein and mRNA as well as the genes involved in the hair inductivity of DP cells. These results suggest that the appearance of miRNAs that suppress the Wnt/β-catenin pathway may be responsible for the loss of ability of DP cells in culture and miR-195-5p is the potential key factor involved in regulating HF inductivity of DP cells.

Highlights

Cultured Dermal papilla (DP) cells can induce hair follicle differentiation in epithelial cells and are required for hair reconstitution to alleviate baldness [1,2,3]
In DP cells, activity of the Wnt pathway is critical for DP cell-mediated hair follicle induction [15,16,17,18]: (1) many studies have explored the hair-inducing ability of DP cells under Wnt/β-catenin signaling activation such as a GSK-3β inhibitor, 6-bromoindirubin-3󸀠-oxime (BIO), and
Our previous study demonstrated that the follicle-inducing ability of cultured DP cells declined with passage [6]

Summary

Introduction

Cultured DP cells can induce hair follicle differentiation in epithelial cells and are required for hair reconstitution to alleviate baldness [1,2,3]. DP cells exhibit aggregative behavior and maintaining follicle inductivity in vivo and in early passage, but further culture results in the loss of these abilities [4, 5]. We have elucidated previously that early-passage cells (passage-4 cells) showed follicle-inducing ability when being injected into the back of NU/NU mice, and latepassage DP cells (passage-10 cells) failed [6]. The Wnt/β-catenin pathway activates genes, including CCN1, CCN2 [12], OVOL1 [13], and Versican [14], which are essential for the maintenance of the trichogenicity of dermal cells. In DP cells, activity of the Wnt pathway is critical for DP cell-mediated hair follicle induction [15,16,17,18]:

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