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J Invest Dermatol. 2017 Oct;137(10):2177-2186. doi: 10.1016/j.jid.2017.06.005. Epub 2017 Jun 20.

TGFβ/SMAD/microRNA-486-3p Signaling Axis Mediates Keratin 17 Expression and Keratinocyte Hyperproliferation in Psoriasis.

Author information

1
Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
2
Institute of Dermatology, Taiyuan City Central Hospital, Shanxi Key Laboratory for Immunological Dermatosis, Taiyuan, China.
3
Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, China. Electronic address: xjwgang@fmmu.edu.cn.

Abstract

Keratin 17 (K17) is strongly expressed in psoriatic lesions but not healthy skin, and plays a crucial role in disease pathogenesis. The mechanism of aberrant K17 expression in psoriasis has not been fully elucidated. MicroRNAs are short, single-stranded, noncoding RNAs that play important roles in regulating gene expression. Psoriasis exhibits a specific microRNA expression profile distinct from that of healthy skin. In this study, we showed that miR-486-3p was markedly reduced in psoriatic epidermis and negatively correlated with the psoriasis area and severity index score. Its expression repressed K17 protein expression and decreased proliferation in a keratinocyte cell line overexpressing K17 (LV K17) compared with controls. Our data indicated that miR-486-3p was regulated by a transforming growth factor-β (TGFβ)/SMAD pathway and possibly mediated the downregulation of K17 protein in TGFβ-treated keratinocytes. Finally, the decreased expression of TGFβ receptor I in psoriatic epidermis inactivated the TGFβ/SMAD pathway, leading to K17 overexpression and cell proliferation. Collectively, our findings demonstrated that a TGFβ/SMAD/miR-486-3p signaling axis in keratinocytes regulated K17 expression and cell proliferation. We conclude that the loss of miR-486-3p in psoriatic epidermis leads to K17 protein overexpression and contributes to the pathogenesis of psoriasis. Overexpression of miR-486-3p may therefore be a therapeutic option for psoriasis.

PMID:
28642156
DOI:
10.1016/j.jid.2017.06.005
[Indexed for MEDLINE]
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