Modulation of Wnt/β-catenin signaling affects the directional differentiation of hair follicle stem cells

Abstract

Aim: The differentiation of hair follicle stem cells (HFSCs) into hair follicle cells has potential clinical applications for cutaneous burns. However, the mechanisms regulating the differentiation of HFSCs into hair follicular papilla or epidermal cells are currently not clear. This study investigated the role of the Wnt/β-catenin pathway and its crosstalk with other signaling components during this differentiation process.

Methods: Lithium chloride (LiCl, 10 mmol/L) and keratinocyte growth factor (KGF, 10 µg/L) were used to induce HFSC differentiation, validated by immunofluorescence analysis. The mRNA expression of β-catenin, adenomatous polyposis coli, glycogen synthase kinase-3β (GSK-3β), axin, and lymphoid enhancer factor-1 after 3, 5, 7, and 9 days were measured to evaluate the role of the Wnt/β-catenin pathway.

Results: During LiCl-induced HFSC differentiation into hair follicle cells, the Wnt/β-catenin signaling pathway was activated and the expression of GSK-3β, a vital component of the degradation compound, was inhibited. This led to increased cytoplasmic β-catenin expression, nuclear translocation, and subsequent target gene transcription. By contrast, KGF induced the differentiation of HFSCs into epidermal cells and did not affect the expression of β-catenin. This data indicates that LiCl and KGF distinctly regulate the differentiation of HFSCs into hair follicle and epidermal cells, respectively. Furthermore, the Wnt/β-catenin signaling pathway is predominantly involved in hair follicle differentiation.

Conclusion: these results demonstrate that LiCl can be used to differentiate HFSCs into hair follicle cells in vitro, which has important therapeutic applications for treating patients with cutaneous damage.

Keywords

Lithium chloride / keratinocyte growth factor / hair follicle stem cells / Wnt/β-catenin signaling pathway

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