Pyridoxine stimulates filaggrin production in human epidermal keratinocytes.

Miyuki Fujishiro,Mio Nakahara,Ichiro Sakata,Shota Takemi,Shoichi Yahagi,Takafumi Sakai

doi:10.1007/s11033-021-06563-y

Abstract

Pyridoxine (PN), one of the vitamers of vitamin B6, plays an important role in the maintenance of epidermal function and is used to treat acne and rough skin. Clinical studies have revealed that PN deficiency causes skin problems such as seborrheic dermatitis and stomatitis. However, the detailed effects of PN and its mechanism of action in epidermal function are poorly understood. In this study, we examined the effects of PN on epidermal function in normal human epidermal keratinocytes and found that PN specifically causes an increase in the expression of profilaggrin mRNA, among marker genes of terminal epidermal differentiation. In addition, PN treatment caused an increase in the production of filaggrin protein in a concentration-dependent manner. Treatment with P2x purinoceptor antagonists, namely, pyridoxal phosphate-6-azo (benzene-2,4-disulfonic acid) tetrasodium salt hydrate and TNP-ATP hydrate, induced an increase in the filaggrin protein levels. Moreover, we showed that elevated filaggrin production induced upon PN treatment was suppressed by ATP (known as P2x purinoceptor agonist). This study is the first to report that PN causes an increase in filaggrin transcription and production, and these results suggest that PN-induced filaggrin production may be a useful target as a daily care component in atopic dermatitis, wherein filaggrin levels are specifically reduced.

Highlights

Vitamin B6 is a multifunctional micronutrient that mediates numerous metabolic processes, including amino acid metabolism, gluconeogenesis, and lipid metabolism
We examined the effects of PN on epidermal function in normal human epidermal keratinocytes and found that PN causes an increase in the expression of profilaggrin mRNA, among marker genes of terminal epidermal differentiation
In order to examine the effects of PN on skin function, we first evaluated the effect of PN on the expression of terminal epidermal differentiation markers in normal human epidermal keratinocytes (NHEKs) using real-time polymerase chain reaction (PCR)

Summary

Introduction

Vitamin B6 is a multifunctional micronutrient that mediates numerous metabolic processes, including amino acid metabolism, gluconeogenesis, and lipid metabolism. Filaggrin is degraded into free amino acids, and the amino acids are further metabolized into urocanic and pyrrolidone carboxylic acids in corneocytes. These are called natural moisturizing factors, and are largely responsible for the ability of the stratum corneum of the skin to remain hydrated at low environmental humidity [10]. In skin diseases such as epidermolytic hyperkeratosis and lamelliform ichthyosis, profilaggrin was reported to accumulate in the skin without being degraded to filaggrin, suggesting that filaggrin is beneficial in maintaining epidermal function [11]. It has been reported that filaggrin expression levels are lower in the skin of individuals with atopic dermatitis [12]

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Results

Conclusion