Oxidative stress activation of miR-125b is part of the molecular switch for Hailey-Hailey disease manifestation

Sonia Manca, Armando Magrelli, Samantha Cialfi, Karine Lefort, Roberto Ambra, Maurizio Alimandi, Gianfranco Biolcati, Daniela Uccelletti, Claudio Palleschi, Isabella Screpanti, Eleonora Candi, Gerry Melino, Marco Salvatore, Domenica Taruscio, Claudio Talora

Research output: Contribution to journalArticle

Abstract

Hailey-Hailey disease (HHD) is an autosomal dominant disorder characterized by suprabasal cutaneous cell separation (acantholysis) leading to the development of erosive and oozing skin lesion. Micro RNAs (miRNAs) are endogenous post-transcriptional modulators of gene expression with critical functions in health and disease. Here, we evaluated whether the expression of specific miRNAs may play a role in the pathogenesis of HHD. Here, we report that miRNAs are expressed in a non-random manner in Hailey-Hailey patients. miR-125b appeared a promising candidate for playing a role in HHD manifestation. Both Notch1 and p63 are part of a regulatory signalling whose function is essential for the control of keratinocyte proliferation and differentiation and of note, the expression of both Notch1 and p63 is downregulated in HHD-derived keratinocytes. We found that both Notch1 and p63 expression is strongly suppressed by miR-125b expression. Additionally, we found that miR-125b expression is increased by an oxidative stress-dependent mechanism. Our data suggest that oxidative stress-mediated induction of miR-125b plays a specific role in the pathogenesis of HHD by regulating the expression of factors playing an important role in keratinocyte proliferation and differentiation.

Original languageEnglish
Pages (from-to)932-937
Number of pages6
JournalExperimental Dermatology
Volume20
Issue number11
DOIs
Publication statusPublished - Nov 2011

Keywords

  • Hailey-Hailey
  • Notch
  • P63
  • Reactive oxygen species
  • Skin disease

ASJC Scopus subject areas

  • Dermatology
  • Molecular Biology
  • Biochemistry

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    Manca, S., Magrelli, A., Cialfi, S., Lefort, K., Ambra, R., Alimandi, M., Biolcati, G., Uccelletti, D., Palleschi, C., Screpanti, I., Candi, E., Melino, G., Salvatore, M., Taruscio, D., & Talora, C. (2011). Oxidative stress activation of miR-125b is part of the molecular switch for Hailey-Hailey disease manifestation. Experimental Dermatology, 20(11), 932-937. https://doi.org/10.1111/j.1600-0625.2011.01359.x