TY - JOUR
T1 - The desmosomal protein desmoglein 1 aids recovery of epidermal differentiation after acute UV light exposure
AU - Johnson, Jodi L.
AU - Koetsier, Jennifer L.
AU - Sirico, Anna
AU - Agidi, Ada T.
AU - Antonini, Dario
AU - Missero, Caterina
AU - Green, Kathleen J.
N1 - Funding Information:
This work was supported by NIH R01 AR041836 and CA122151, with partial support from AR43380 to KJG. Additional support was provided by the JL Mayberry endowment to KJG. The financial support of Telethon, Italy (GGP09230), of the European ERA-Net Research Program on Rare Diseases (E-Rare-2; Skindev), and of the Italian Association for Cancer Research (AIRC; IG5348) to CM is gratefully acknowledged. JLJ’s salary was supported by a Research Career Development Award through the Dermatology Foundation, and salary and some research supplies were supported by a NIH/NCI Ruth L Kirschstein Training Grant through Northwestern University’s Robert H Lurie Comprehensive Cancer Center (T32 CA070085-14) “Signal Transduction in Cancer.” ATA’s stipend and some research supplies were supported through the Northwestern University Lurie Comprehensive Cancer Center’s Continuing Umbrella of Research Experience (CURE) Summer Program for Underserved Students, a supplement to P30 CA060553. In addition, this research was supported in part by resources provided by the Northwestern University Skin Disease Research Center (NIH/NIAMS 5P30AR057216-02). Any opinions, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the Northwestern University Skin Disease Research Center or the NIH/NIAMS.
PY - 2014/8
Y1 - 2014/8
N2 - Epidermal structure is damaged by exposure to UV light, but the molecular mechanisms governing structural repair are largely unknown. UVB (290-320 nm wavelengths) exposure before induction of differentiation reduced expression of differentiation-associated proteins, including desmoglein 1 (Dsg1), desmocollin 1 (Dsc1), and keratins 1 and 10 (K1/K10), in a dose-dependent manner in normal human epidermal keratinocytes (NHEKs). The UVB-induced reduction in both Dsg1 transcript and protein was associated with reduced binding of the p63 transcription factor to previously unreported enhancer regulatory regions of the Dsg1 gene. As Dsg1 promotes epidermal differentiation in addition to participating in cell-cell adhesion, the role of Dsg1 in aiding differentiation after UVB damage was tested. Compared with controls, depleting Dsg1 via short hairpin RNA resulted in further reduction of Dsc1 and K1/K10 expression in monolayer NHEK cultures and in abnormal epidermal architecture in organotypic skin models recovering from UVB exposure. Ectopic expression of Dsg1 in keratinocyte monolayers rescued the UVB-induced differentiation defect. Treatment of UVB-exposed monolayer or organotypic cultures with trichostatin A, a histone deacetylase inhibitor, partially restored differentiation marker expression, suggesting a potential therapeutic strategy for reversing UV-induced impairment of epidermal differentiation after acute sun exposure.
AB - Epidermal structure is damaged by exposure to UV light, but the molecular mechanisms governing structural repair are largely unknown. UVB (290-320 nm wavelengths) exposure before induction of differentiation reduced expression of differentiation-associated proteins, including desmoglein 1 (Dsg1), desmocollin 1 (Dsc1), and keratins 1 and 10 (K1/K10), in a dose-dependent manner in normal human epidermal keratinocytes (NHEKs). The UVB-induced reduction in both Dsg1 transcript and protein was associated with reduced binding of the p63 transcription factor to previously unreported enhancer regulatory regions of the Dsg1 gene. As Dsg1 promotes epidermal differentiation in addition to participating in cell-cell adhesion, the role of Dsg1 in aiding differentiation after UVB damage was tested. Compared with controls, depleting Dsg1 via short hairpin RNA resulted in further reduction of Dsc1 and K1/K10 expression in monolayer NHEK cultures and in abnormal epidermal architecture in organotypic skin models recovering from UVB exposure. Ectopic expression of Dsg1 in keratinocyte monolayers rescued the UVB-induced differentiation defect. Treatment of UVB-exposed monolayer or organotypic cultures with trichostatin A, a histone deacetylase inhibitor, partially restored differentiation marker expression, suggesting a potential therapeutic strategy for reversing UV-induced impairment of epidermal differentiation after acute sun exposure.
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U2 - 10.1038/jid.2014.124
DO - 10.1038/jid.2014.124
M3 - Article
C2 - 24594668
AN - SCOPUS:84904465324
VL - 134
SP - 2154
EP - 2162
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
SN - 0022-202X
IS - 8
ER -
