Skip to main content
SpringerLink
Log in

Pyridoxine stimulates filaggrin production in human epidermal keratinocytes

  • Original Article
  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Rosenberg IH (2012) A history of the isolation and identification of vitamin B(6). Ann Nutr Metab 61(3):236–238

    Article  CAS  Google Scholar 

  2. Schereiner AW et al (1952) Seborrheic dermatitis; a local metabolic defect involving pyridoxine. J Lab Clin Med 40(1):121–130

    CAS  PubMed  Google Scholar 

  3. Lakshmi AV, Ramalakshmi BA (1998) Effect of pyridoxine or riboflavin supplementation on plasma homocysteine levels in women with oral lesions. Natl Med J India 11(4):171–172

    CAS  PubMed  Google Scholar 

  4. Effersoe H (1954) The effect of topical application of pyridoxine ointment on the rate of sebaceous secretion in patients with seborrheic dermatitis. Acta Derm Venereol 34(3):272–278

    CAS  PubMed  Google Scholar 

  5. Trezise DJ et al (1994) P2 purinoceptor antagonist properties of pyridoxal-5-phosphate. Eur J Pharmacol 259(3):295–300

    Article  CAS  Google Scholar 

  6. Dale BA, Holbrook KA, Steinert PM (1978) Assembly of stratum corneum basic protein and keratin filaments in macrofibrils. Nature 276(5689):729–731

    Article  CAS  Google Scholar 

  7. Resing KA, Walsh KA, Dale BA (1984) Identification of two intermediates during processing of profilaggrin to filaggrin in neonatal mouse epidermis. J Cell Biol 99(4 Pt 1):1372–1378

    Article  CAS  Google Scholar 

  8. Lonsdale-Eccles JD et al (1984) High-molecular-weight precursor of epidermal filaggrin and hypothesis for its tandem repeating structure. Biochemistry 23(6):1239–1245

    Article  CAS  Google Scholar 

  9. Scott IR, Harding CR (1981) Studies on the synthesis and degradation of a high molecular weight, histidine-rich phosphoprotein from mammalian epidermis. Biochim Biophys Acta 669(1):65–78

    Article  CAS  Google Scholar 

  10. Scott IR, Harding CR (1986) Filaggrin breakdown to water binding compounds during development of the rat stratum corneum is controlled by the water activity of the environment. Dev Biol 115(1):84–92

    Article  CAS  Google Scholar 

  11. Goldman RD, Steinert PM (1990) Cellular and molecular biology of intermediate filaments. Plenum Press, New York, pp 393–412

    Book  Google Scholar 

  12. Seguchi T et al (1996) Decreased expression of filaggrin in atopic skin. Arch Dermatol Res 288(8):442–446

    Article  CAS  Google Scholar 

  13. Thacher SM, Rice RH (1985) Keratinocyte-specific transglutaminase of cultured human epidermal cells: relation to cross-linked envelope formation and terminal differentiation. Cell 40(3):685–695

    Article  CAS  Google Scholar 

  14. Dale BA et al (1985) Expression of epidermal keratins and filaggrin during human fetal skin development. J Cell Biol 101(4):1257–1269

    Article  CAS  Google Scholar 

  15. Steven AC et al (1990) Biosynthetic pathways of filaggrin and loricrin–two major proteins expressed by terminally differentiated epidermal keratinocytes. J Struct Biol 104(1–3):150–162

    Article  CAS  Google Scholar 

  16. Mills AA et al (1999) p63 is a p53 homologue required for limb and epidermal morphogenesis. Nature 398(6729):708–713

    Article  CAS  Google Scholar 

  17. Blanpain C et al (2006) Canonical notch signaling functions as a commitment switch in the epidermal lineage. Genes Dev 20(21):3022–3035

    Article  CAS  Google Scholar 

  18. Okuyama R et al (2004) High commitment of embryonic keratinocytes to terminal differentiation through a Notch1-caspase 3 regulatory mechanism. Dev Cell 6(4):551–562

    Article  CAS  Google Scholar 

  19. Yuspa SH et al (1989) Expression of murine epidermal differentiation markers is tightly regulated by restricted extracellular calcium concentrations in vitro. J Cell Biol 109(3):1207–1217

    Article  CAS  Google Scholar 

  20. Otsuka A et al (2014) Possible new therapeutic strategy to regulate atopic dermatitis through upregulating filaggrin expression. J Allergy Clin Immunol 133(1):139–146

    Article  CAS  Google Scholar 

  21. Palmer CN et al (2006) Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis. Nat Genet 38(4):441–446

    Article  CAS  Google Scholar 

  22. Sandilands A et al (2007) Comprehensive analysis of the gene encoding filaggrin uncovers prevalent and rare mutations in ichthyosis vulgaris and atopic eczema. Nat Genet 39(5):650–654

    Article  CAS  Google Scholar 

  23. Howell MD et al (2009) Cytokine modulation of atopic dermatitis filaggrin skin expression. J Allergy Clin Immunol 124(3 Suppl 2):R7–R12

    Article  CAS  Google Scholar 

  24. Milner P et al (1990) Rapid release of endothelin and ATP from isolated aortic endothelial cells exposed to increased flow. Biochem Biophys Res Commun 170(2):649–656

    Article  CAS  Google Scholar 

  25. Hansen M et al (1993) Intercellular calcium signaling induced by extracellular adenosine 5’-triphosphate and mechanical stimulation in airway epithelial cells. J Cell Sci 106(Pt 4):995–1004

    Article  CAS  Google Scholar 

  26. Ferguson DR, Kennedy I, Burton TJ (1997) ATP is released from rabbit urinary bladder epithelial cells by hydrostatic pressure changes–a possible sensory mechanism? J Physiol 505(Pt 2):503–511

    Article  CAS  Google Scholar 

  27. Lambrecht G (2000) Agonists and antagonists acting at P2X receptors: selectivity profiles and functional implications. Naunyn Schmiedebergs Arch Pharmacol 362(4–5):340–350

    Article  CAS  Google Scholar 

  28. North RA, Surprenant A (2000) Pharmacology of cloned P2X receptors. Annu Rev Pharmacol Toxicol 40:563–580

    Article  CAS  Google Scholar 

  29. Pillai S, Bikle DD (1992) Adenosine triphosphate stimulates phosphoinositide metabolism, mobilizes intracellular calcium, and inhibits terminal differentiation of human epidermal keratinocytes. J Clin Invest 90(1):42–51

    Article  CAS  Google Scholar 

  30. Dixon CJ et al (1999) Regulation of epidermal homeostasis through P2Y2 receptors. Br J Pharmacol 127(7):1680–1686

    Article  CAS  Google Scholar 

  31. Greig AV et al (2003) Purinergic receptors are part of a signaling system for keratinocyte proliferation, differentiation, and apoptosis in human fetal epidermis. J Invest Dermatol 121(5):1145–1149

    Article  CAS  Google Scholar 

  32. Burrell HE et al (2003) Human keratinocytes express multiple P2Y-receptors: evidence for functional P2Y1, P2Y2, and P2Y4 receptors. J Invest Dermatol 120(3):440–447

    Article  CAS  Google Scholar 

  33. Burrell HE et al (2005) Human keratinocytes release ATP and utilize three mechanisms for nucleotide interconversion at the cell surface. J Biol Chem 280(33):29667–29676

    Article  CAS  Google Scholar 

  34. Inoue K et al (2005) Characterization of multiple P2X receptors in cultured normal human epidermal keratinocytes. J Invest Dermatol 124(4):756–763

    Article  CAS  Google Scholar 

  35. Khakh BS et al (2001) International union of pharmacology. XXIV. Current status of the nomenclature and properties of P2X receptors and their subunits. Pharmacol Rev 53(1):107–118

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Area of Regulatory Biology, Division of Life Science, Graduate School of Science and Engineering, Saitama University, 255 Shimo-ohkubo, Sakuraku, Saitama, 338-8570, Japan

    Miyuki Fujishiro, Shota Takemi, Mio Nakahara & Ichiro Sakata

  2. Nikkol Group Cosmos Technical Center Co., Ltd., 3-24-3 Hasune, Itabashiku, Tokyo, 174-0046, Japan

    Miyuki Fujishiro & Shoichi Yahagi

  3. Saitama University, 255 Shimo-okubo, Sakura-ku, Saitama, 338-8570, Japan

    Takafumi Sakai

  4. Area of Life-NanoBio, Division of Strategy Research, Graduate School of Science and Engineering, Saitama University, 255 Shimo-okubo, Sakura-ku, Saitama, 338-8570, Japan

    Ichiro Sakata

Authors
  1. Miyuki Fujishiro
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shoichi Yahagi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shota Takemi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mio Nakahara
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Takafumi Sakai
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ichiro Sakata
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

MF collected the data and wrote the manuscript. SY and MN collected the data. ST wrote the manuscript. TS and IS involved in direction of experiment and writing the manuscript.

Corresponding author

Correspondence to Ichiro Sakata.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Informed consent

The authors declare that they consent for publication of this study.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (EPS 3773 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Fujishiro, M., Yahagi, S., Takemi, S. et al. Pyridoxine stimulates filaggrin production in human epidermal keratinocytes. Mol Biol Rep 48, 5513–5518 (2021). https://doi.org/10.1007/s11033-021-06563-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-021-06563-y

Keywords

Search

Navigation