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Knockdown of FOXA2 Impairs Hair-Inductive Activity of Cultured Human Follicular Keratinocytes.

ABSTRACT: Reciprocal interactions between hair-inductive dermal cells and epidermal cells are essential for de novo genesis of hair follicles. Recent studies have shown that outer root sheath (ORS) follicular keratinocytes can be expanded in vitro, but the cultured cells often lose receptivity to hair-inducing dermal signals. In this study, we first investigated whether the hair-inductive activity (trichogenicity) of cultured human ORS follicular keratinocytes was correlated with the cultivation period. ORS follicular keratinocytes from the scalp were cultured for 3, 4, 5, or 6 weeks and were then implanted into nude mice along with freshly isolated neonatal mouse dermal cells. We observed that the trichogenicity of the implanted ORS cells was inversely correlated with their cultivation period. These initial findings prompted us to investigate the differentially expressed genes between the short-term (20 days) and long-term (42 days) cultured ORS cells, trichogenic and non-trichogenic, respectively, by microarray analysis. We found that forkhead box protein A2 (FOXA2) was the most up-regulated transcription factor in the trichogenic ORS cells. Thus, we investigated whether the trichogenicity of the cells was affected by FOXA2 expression. We found a significant decrease in the number of induced hair follicles when the ORS cells were transfected with a FOXA2 small interfering RNA versus control small interfering RNA. Taken together, our data strongly suggest that FOXA2 significantly influences the trichogenicity of human ORS cells.

SUBMITTER: Bak SS

PROVIDER: S-EPMC7578224 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Knockdown of FOXA2 Impairs Hair-Inductive Activity of Cultured Human Follicular Keratinocytes.

Bak Soon-Sun SS Park Jung Min JM Oh Ji Won JW Kim Jung Chul JC Kim Moon Kyu MK Sung Young Kwan YK

Frontiers in cell and developmental biology 20201008

Reciprocal interactions between hair-inductive dermal cells and epidermal cells are essential for <i>de novo</i> genesis of hair follicles. Recent studies have shown that outer root sheath (ORS) follicular keratinocytes can be expanded <i>in vitro</i>, but the cultured cells often lose receptivity to hair-inducing dermal signals. In this study, we first investigated whether the hair-inductive activity (trichogenicity) of cultured human ORS follicular keratinocytes was correlated with the cultiva ...[more]

PMID: 33117803

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Project description:Folate nutrition is critical in humans and a high dietary folate intake is associated with a diminished risk of many types of cancer. Both synthetic folic acid and the most biologically abundant extracellular reduced folate, 5-methyltetrahydrofolate, are degraded under conditions of ultraviolet radiation (UVR) exposure. Skin is a proliferative tissue with increased folate nutrient demands due to a dependence upon continuous epidermal cell proliferation and differentiation to maintain homeostasis. Regions of skin are also chronically exposed to UVR, which penetrates to the actively dividing basal layer of the epidermis, increasing the folate nutrient demands in order to replace folate species degraded by UVR exposure and to supply the folate cofactors required for repair of photo-damaged DNA. Localized folate deficiencies of skin are a likely consequence of UVR exposure. We report here a cultured keratinocyte model of folate deficiency that has been applied to examine possible effects of folate nutritional deficiencies in skin. Utilizing this model, we were able to quantify the concentrations of key intracellular folate species during folate depletion and repletion. We investigated the hypotheses that the genomic instability observed under conditions of folate deficiency in other cell types extends to skin, adversely effecting cellular capacity to handle UVR insult and that optimizing folate levels in skin is beneficial in preventing or repairing the pro-carcinogenic effects of UVR exposure. Folate restriction leads to rapid depletion of intracellular reduced folates resulting in S-phase growth arrest, increased levels of inherent DNA damage, and increased uracil misincorporation into DNA, without a significant losses in overall cellular viability. Folate depleted keratinocytes were sensitized toward UVR induced apoptosis and displayed a diminished capacity to remove DNA breaks resulting from both photo and oxidative DNA damage. Thus, folate deficiency creates a permissive environment for genomic instability, an early event in the process of skin carcinogenesis. The effects of folate restriction, even in severely depleted, growth-arrested keratinocytes, were reversible by repletion with folic acid. Overall, these results indicate that skin health can be positively influenced by optimal folate nutriture.

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Knockdown of FOXA2 Impairs Hair-Inductive Activity of Cultured Human Follicular Keratinocytes.

Publications

Knockdown of FOXA2 Impairs Hair-Inductive Activity of Cultured Human Follicular Keratinocytes.

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