Biochemical and Biophysical Research Communications, Vol.532, No.4, 626-632, 2020
Upregulation of hsa-miR-31-3p induced by ultraviolet affects keratinocytes permeability barrier by targeting CLDN1
Chronic actinic dermatitis (CAD) is a photoallergic skin disease with complicated pathogenesis. However, skin barrier dysfunction may be involved according to clinical manifestation. To investigate the mechanism of CAD barrier dysfunction, noninvasive detection of skin barrier and small RNA sequencing were carried out. Quantitative real-time PCR (qRT-PCR) was used to evaluate the expression levels of hsa-miR31-3p and CLDN1. The correlation between hsa-miR-31-3p and CAD severity was explored. Further, dualluciferase reporter assay was performed to identify the relationship between hsa-miR-31-3p and CLDN1. In addition, expression of hsa-miR-31-3p was detected after ultraviolet (UV) irradiation. Influences of hsa-miR-31-3p on primary human keratinocytes barrier were assessed by FITC-Dextran permeability assay. Moreover, western blot was used to detect the expression of claudin-1, filaggrin, loricrin and involucrin. Our results showed that transepidermal water loss (TEWL) significantly increased in CAD, while stratum corneum hydration (SCH) significantly decreased. The expression of hsa-miR-31-3p was up-regulated in CAD while CLDN1 was down-regulated. Hsa-miR-31-3p was correlated with TEWL, UV-MED (minimal erythema dose) and clinical severity scores of CAD (CSS-CAD). Dual-luciferase reporter assay confirmed that hsa-miR-31-3p targeted the 3'UTR region of CLDN1. Moreover, hsa-miR-31-3p was induced by UVB (0-30 mJ/cm(2)) and UVA (0-4 J/cm(2)). Furthermore, overexpression of hsa-miR-31-3p increased FITC-Dextran flux of primary human keratinocytes and reduced the expression of claudin-1, filaggrin, loricrin and involucrin. In conclusion, we demonstrated that hsa-miR-31-3p induced by UV was correlated with CAD severity, which played an important role in regulating keratinocytes permeability barrier through targeting CLDN1. (C) 2020 Elsevier Inc. All rights reserved.