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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.

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Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
Institute of Dermatology, Taiyuan City Central Hospital, Shanxi Key Laboratory for Immunological Dermatosis, Taiyuan, China.
Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, China. Electronic address:


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.

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