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Oxidative stress activation of miR‐125b is part of the molecular switch for Hailey–Hailey disease manifestation
Author(s) -
Manca Sonia,
Magrelli Armando,
Cialfi Samantha,
Lefort Karine,
Ambra Roberto,
Alimandi Maurizio,
Biolcati Gianfranco,
Uccelletti Daniela,
Palleschi Claudio,
Screpanti Isabella,
Candi Eleonora,
Melino Gerry,
Salvatore Marco,
Taruscio Domenica,
Talora Claudio
Publication year - 2011
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/j.1600-0625.2011.01359.x
Subject(s) - oxidative stress , hailey–hailey disease , disease , oxidative phosphorylation , cancer research , chemistry , medicine , biochemistry
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.