Abstract
BackgroundDysfunction of the DNA methylation was associated with stem cell reprogramming. Moreover, DNA methyltransferase 1 (DNMT1) deficiency was involved in the differentiation of hair follicle stem cell (HFSc), but the molecular mechanisms remain unknown.MethodsHFSc from human scalp tissues were isolated and cultured. The oil red O staining was used to observe the adipogenesis. The interaction relationship between microRNA (miR)-214-3p and mitogen-activated protein kinase 1 (MAPK1) was accessed by dual-luciferase reporter gene assay. The methylation level of miR-214-3p promoter was detected by methylation-specific PCR and the enrichment of DNMT1 in miR-214-3p promoter by chromatin immunoprecipitation assay. A mouse model of trauma was established to observe the skin regeneration at 0, 6, and 14 days.ResultsExpression of DNMT1 and MAPK1 was increased in the HFSc, while the expression of miR-214-3p was reduced. Moreover, DNMT1 inhibited the expression of miR-214-3p by promoting the promoter methylation of miR-214-3p. Overexpression of DNMT1 could reduce the expression of miR-214-3p, but increase the expression of MAPK1 and the extent of extracellular signal regulated kinase (ERK)1/2 phosphorylation, leading to enhanced adipogenic differentiation. Importantly, DNMT1 promoted skin regeneration in vivo. Conversely, overexpression of miR-214-3p could reverse the effects of DNMT1 on adipogenesis of HFSc.ConclusionDNMT1 promotes adipogenesis of HFSc by mediating miR-214-3p/MAPK1/p-ERK1/2 axis. This study may provide novel biomarkers for the potential application in stem cell therapy.
Highlights
Dysfunction of the DNA methylation was associated with stem cell reprogramming
DNA methyltransferase 1 (DNMT1) promotes differentiation of hair follicle stem cell (HFSc) into adipogenic lineages In order to demonstrate the effect of DNMT1 in the differentiation of HFSc, the HFScs were induced differentiation into adipogenic lineages
These data indicated that DNMT1 promotes HFSc differentiate into adipogenic lineages
Summary
Dysfunction of the DNA methylation was associated with stem cell reprogramming. DNA methyltransferase 1 (DNMT1) deficiency was involved in the differentiation of hair follicle stem cell (HFSc), but the molecular mechanisms remain unknown. Differentiation of epithelial cells is the key process of epidermal wound repair. Diverse stem cells of the hair follicle (HF) and interfollicular epidermis have been found to accumulate at the site of skin injury [5]. Emerging studies have revealed important functions of DNA methylation in skin biology such as it can regulate HFSc differentiation [8, 9]. DNMT1 plays a central role in DNA methylation and can inhibit several microRNAs (miRNAs) and accumulates in the promoter regions of miRNAs [10]. The role of DNMT1 in wound healing and skin regeneration remains poorly understood
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