Nicotinamide attenuates aquaporin 3 overexpression induced by retinoic acid through inhibition of EGFR/ERK in cultured human skin keratinocytes

  • Authors:
    • Xiuzu Song
    • Aie xu
    • Wei Pan
    • Brittany Wallin
    • Rebecca Kivlin
    • Shan Lu
    • Cong Cao
    • Zhigang Bi
    • Yinsheng Wan
  • View Affiliations

  • Published online on: August 1, 2008     https://doi.org/10.3892/ijmm_00000013
  • Pages: 229-236
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

The most common adverse effects that are related to all-trans retinoic acid (atRA) treatment are irritation and dryness of the skin. atRA therapy is reported to impair barrier function as achieved by trans-epidermal water loss (TEWL). Treatment with nicotinamide prior to initiation of atRA therapy provides additional barrier protection and thus reduces susceptibility of retinoic acid. Our previous studies showed that atRA upregulates aquaporin 3 (AQP3) in cultured human skin keratinocytes and fibroblasts. Others have demonstrated that in atopic dermatitis, overexpression of AQP3 is linked to elevated TEWL and that nicotinamide treatment reduces skin TEWL. In this study, we observed that while atRA upregulates AQP3 expression in cultured human skin keratinocytes (HaCaT cells), nicotinamide attenuates the effect of atRA in a concentration-dependent manner. atRA treatment induces EGFR and ERK activation. PD153035, an EGFR inhibitor, and U0126, an ERK inhibitor, inhibit atRA-induced upregulation of AQP3. Nicotinamide also inhibits atRA-induced activation of EGFR/ERK signal transduction and decreases water permeability by downregulating AQP3 expression. Collectively, our results indicate that the effect of atRA on AQP3 expression is at least partly mediated by EGFR/ERK signaling in cultured human skin keratinocytes. Nicotinamide attenuates atRA-induced AQP3 expression through inhibition of EGFR/ERK signal transduction and eventually decreases water permeability and water loss. Our study provides insights into the molecular mechanism through which nicotinamide reverses the side effects of dryness in human skin after treatment with atRA.

Related Articles

Journal Cover

August 2008
Volume 22 Issue 2

Print ISSN: 1107-3756
Online ISSN:1791-244X

Sign up for eToc alerts

Recommend to Library

The Cancer Story
Copy and paste a formatted citation
x
Spandidos Publications style
Song X, xu A, Pan W, Wallin B, Kivlin R, Lu S, Cao C, Bi Z and Wan Y: Nicotinamide attenuates aquaporin 3 overexpression induced by retinoic acid through inhibition of EGFR/ERK in cultured human skin keratinocytes. Int J Mol Med 22: 229-236, 2008
APA
Song, X., xu, A., Pan, W., Wallin, B., Kivlin, R., Lu, S. ... Wan, Y. (2008). Nicotinamide attenuates aquaporin 3 overexpression induced by retinoic acid through inhibition of EGFR/ERK in cultured human skin keratinocytes. International Journal of Molecular Medicine, 22, 229-236. https://doi.org/10.3892/ijmm_00000013
MLA
Song, X., xu, A., Pan, W., Wallin, B., Kivlin, R., Lu, S., Cao, C., Bi, Z., Wan, Y."Nicotinamide attenuates aquaporin 3 overexpression induced by retinoic acid through inhibition of EGFR/ERK in cultured human skin keratinocytes". International Journal of Molecular Medicine 22.2 (2008): 229-236.
Chicago
Song, X., xu, A., Pan, W., Wallin, B., Kivlin, R., Lu, S., Cao, C., Bi, Z., Wan, Y."Nicotinamide attenuates aquaporin 3 overexpression induced by retinoic acid through inhibition of EGFR/ERK in cultured human skin keratinocytes". International Journal of Molecular Medicine 22, no. 2 (2008): 229-236. https://doi.org/10.3892/ijmm_00000013