LncRNA-XIST promotes dermal papilla induced hair follicle regeneration by targeting miR-424 to activate hedgehog signaling

Alopecia is a highly prevalent disease characterizing by the loss of hair. Dermal papilla (DP) cells are the inducer of hair follicle regeneration, and in vitro three-dimensional (3D) culturing DP cells have been proven to induce hair follicle regeneration. However, the molecular mechanisms behind t...

Full description

Saved in:
Bibliographic Details
Published in:Cellular signalling 2020-08, Vol.72, p.109623-109623, Article 109623
Main Authors: Lin, Bo-Jie, Zhu, Jiang-Ying, Ye, Jun, Lu, Si-Ding, Liao, Ming-De, Meng, Xu-Chang, Yin, Guo-Qian
Format: Article
Language:English
Subjects:
Dermal papilla
Hair follicle regeneration
Hedgehog signaling pathway
lncRNA-XIST
miR-424
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Alopecia is a highly prevalent disease characterizing by the loss of hair. Dermal papilla (DP) cells are the inducer of hair follicle regeneration, and in vitro three-dimensional (3D) culturing DP cells have been proven to induce hair follicle regeneration. However, the molecular mechanisms behind the regulation of 3D culturing DP cells remain unclear. 3D-cultivated DP cells were used as in vitro cell model. DP sphere xenograft to nude mice was performed for in vivo study of hair follicle regeneration. qRT-PCR, Western blotting, and immunofluorescence were used for detecting the level of XIST, miR-424 and Hedgehog pathway-related proteins, respectively. H&E staining was used to examine hair neogenesis. Cell viability, proliferation and ALP activity were measured by MTT, CCK-8 and ELISA assays, respectively. Luciferase assays were used for studying molecular regulation between XIST, miR-424 and Shh 3′UTR. XIST and Shh were up-regulated, and miR-424 was down-regulated in 3D DP cells. Molecular regulation studies suggested that XIST sponged miR-424 to promote Shh expression. Knockdown of XIST suppressed DP cell activity, cell proliferation, ALP activity and the expression of other DP markers by sponging miR-424. Knockdown of XIST suppressed Shh mediated hedgehog signaling by targeting miR-424. Moreover, the knockdown of XIST inhibited DP sphere induced in vivo hair follicle regeneration and hair development. XIST sponges miR-424 to promote Shh expression, thereby activating hedgehog signaling and facilitating DP mediated hair follicle regeneration. •The expression of XIST and Shh is up-regulated, but miR-424 expression is down-regulated in 3D culturing of DP cells.•XIST promotes Shh gene expression via sponging miR-424.•Knockdown of XIST results in suppression of viability, proliferation and DP marker expression in DP cells by targeting miR-424.•Knockdown of XIST suppresses Hedgehog signaling by targeting miR-424 to inhibit Shh expression in DP cells.•Knockdown of XIST suppresses DP cells-mediated hair follicle regeneration and hair formation in nude mice.
ISSN:0898-6568
1873-3913
DOI:10.1016/j.cellsig.2020.109623