Amphiregulin promotes hair regeneration of skin-derived precursors via the PI3K and MAPK pathways.
Cell Prolif
; 54(9): e13106, 2021 Sep.
Article
em En
| MEDLINE
| ID: mdl-34382262
ABSTRACT
OBJECTIVES:
There are significant clinical challenges associated with alopecia treatment, including poor efficiency of related drugs and insufficient hair follicles (HFs) for transplantation. Skin-derived precursors (SKPs) exhibit great potential as stem cell-based therapies for hair regeneration; however, the proliferation and hair-inducing capacity of SKPs gradually decrease during culturing. MATERIALS ANDMETHODS:
We describe a 3D co-culture system accompanied by kyoto encyclopaedia of genes and genomes and gene ontology enrichment analyses to determine the key factors and pathways that enhance SKP stemness and verified using alkaline phosphatase assays, Ki-67 staining, HF reconstitution, Western blot and immunofluorescence staining. The upregulated genes were confirmed utilizing corresponding recombinant protein or small-interfering RNA silencing in vitro, as well as the evaluation of telogen-to-anagen transition and HF reconstitution in vivo.RESULTS:
The 3D co-culture system revealed that epidermal stem cells and adipose-derived stem cells enhanced SKP proliferation and HF regeneration capacity by amphiregulin (AREG), with the promoted stemness allowing SKPs to gain an earlier telogen-to-anagen transition and high-efficiency HF reconstitution. By contrast, inhibitors of the phosphoinositide 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways downstream of AREG signalling resulted in diametrically opposite activities.CONCLUSIONS:
By exploiting a 3D co-culture model, we determined that AREG promoted SKP stemness by enhancing both proliferation and hair-inducing capacity through the PI3K and MAPK pathways. These findings suggest AREG therapy as a potentially promising approach for treating alopecia.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Regeneração
/
Pele
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Transdução de Sinais
/
Folículo Piloso
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Fosfatidilinositol 3-Quinases
/
Proteínas Quinases Ativadas por Mitógeno
/
Anfirregulina
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article