1. miR-21-3p/IL-22 Axes Are Major Drivers of Psoriasis Pathogenesis by Modulating Keratinocytes Proliferation-Survival Balance and Inflammatory Response.
- Author
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Abdallah F, Henriet E, Suet A, Arar A, Clemençon R, Malinge JM, Lecellier G, Baril P, and Pichon C
- Subjects
- Animals, Cell Proliferation genetics, Cell Proliferation physiology, Down-Regulation, Keratinocytes metabolism, Mice, MicroRNAs metabolism, Psoriasis drug therapy, Skin metabolism, Transcriptional Activation immunology, Up-Regulation, Interleukin-22, Inflammation immunology, Interleukins metabolism, MicroRNAs genetics, Psoriasis metabolism
- Abstract
Psoriasis is a chronic inflammatory skin disease that is mediated by complex crosstalk between immune cells and keratinocytes (KCs). Emerging studies have showed a specific psoriatic microRNAs signature, in which miR-21 is one of the most upregulated and dynamic miRNAs. In this study, we focused our investigations on the passenger miR-21-3p strand, which is poorly studied in skin and in psoriasis pathogenesis. Here, we showed the upregulation of miR-21-3p in an IMQ-induced psoriasiform mouse model. This upregulation was correlated with IL-22 expression and functionality, both in vitro and in vivo, and it occurred via STAT3 and NF-κB signaling. We identified a network of differentially expressed genes involved in abnormal proliferation control and immune regulatory genes implicated in the molecular pathogenesis of psoriasis in response to miR-21-3p overexpression in KCs. These results were confirmed by functional assays that validated the proliferative potential of miR-21-3p. All these findings highlight the importance of miR-21-3p, an underestimated miRNA, in psoriasis and provide novel molecular targets for therapeutic purposes.
- Published
- 2021
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