Down-regulation of miR-223 contributes to the formation of Gottron's papules in dermatomyositis via the induction of PKCɛ.

Abstract

BACKGROUND:

Dermatomyositis (DM) is characterized by skin manifestations accompanying and preceding muscle weakness. Gottron's papules, one of the skin manifestations, are of great diagnostic value because they are specific to DM. However, the pathogenesis of Gottron's papules remains unclear.

OBJECTIVES:

We investigated the expression pattern of miRNAs in Gottron's papules of DM patients and evaluated the possibility that miRNAs play a role in its pathogenesis.

MATERIALS AND METHODS:

miRNAs were extracted from skin tissues and sera of patients with DM, clinically amyopathic DM (CADM) and healthy controls. To identify pathogenic miRNAs, we performed miRNA PCR array analysis. The results were confirmed by in situ hybridization, immunohistochemistry, immunoblotting and transient transfection of siRNAs or miRNA inhibitors.

RESULTS:

PCR array analysis using tissue miRNAs demonstrated the miR-223 level was markedly decreased in Gottron's papules of DM and CADM in vivo, but not in psoriasis skin. The protein expression of PKCɛ, a predicted target of miR-223, was increased in DM/CADM skin. The transfection of a specific inhibitor of miR-223 in keratinocytes led to up-regulation of the PKCɛ protein, and resulted in increased cell proliferation. On the other hand, cell numbers were significantly decreased when cells were transfected with siRNA for PKCɛ. The serum miR-223 concentration was decreased in DM/PM patients, particularly in CADM patients, compared with healthy controls.

CONCLUSIONS:

A decreased miR-223 expression and the subsequently increased PKCɛ levels may therefore play a key role in the pathogenesis of Gottron's papules.

• Authors: Kuniko Inoue, Masatoshi Jinnin, Keitaro Yamane, Takamitsu Makino, Ikko Kajihara, Katsunari Makino, Norithosi Honda, Wakana Nakayama, Satoshi Fukushima, Hironobu Ihn
• Journal: European journal of dermatology : EJD (Eur J Dermatol) Vol. 23 Issue 2 Pg. 160-7 (Apr 01 2013) ISSN: 1952-4013 [Electronic] France
• PMID: 23557915 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• MIRN223 microRNA, human
• MicroRNAs
• RNA, Small Interfering
• Protein Kinase C-epsilon

Topics

• Cell Proliferation
• Cells, Cultured
• Dermatomyositis (blood, metabolism, pathology)
• Down-Regulation
• Gene Expression Profiling
• Humans
• Keratinocytes
• MicroRNAs (blood, genetics, metabolism)
• Oligonucleotide Array Sequence Analysis
• Protein Kinase C-epsilon (metabolism)
• RNA, Small Interfering
• Transfection