MiR-124-3p Delivered Using Exosomes Attenuates the Keratinocyte Response to IL-17A Stimulation in Psoriasis.

Abstract

Methods NHEKs, HaCaT cells, and HEK 293T cells were treated with IL-17A. CCK-8 assays were performed to detect cell activity, and immunofluorescence staining and Western blotting were performed to detect the protein expression of STAT3. After isolation of exosomes via ultracentrifugation, the contents of miR-124-3p and oxidative stress markers such as superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) in keratinocytes were measured. Subsequently, transcriptomic analysis was performed using RNA-seq. Data were analysed by using the “edgeR” package within R. After verifying the abnormally expressed genes stimulated by IL-17A, a dual luciferase reporter assay was used to determine the interaction between miR-124-3p and STAT3. Finally, BALB/c mice were used to establish a psoriasis model for analysis. The effect of elevated miR-124-3p on the psoriasis mouse model was determined by exosomal delivery of miR-124-3p. Results IL-17 intervention enhanced the cell activity of keratinocytes (P < 0.05). miR-124-3p was identified by RNA-seq as one of the differentially expressed miRNAs stimulated by IL-17A. miR-124-3p overexpression induced decreased STAT3 and MDA levels, increased SOD and GSH-Px levels in keratinocytes, and alleviated emergency responses of sclerosis damage (P < 0.05). The dual luciferase reporter assay results confirmed that STAT3 was regulated by miR-124-3p in a targeted manner (P < 0.05). Finally, miR-124-3p delivered by exosomes effectively alleviated the pathological manifestations and oxidative stress responses of psoriatic mice. Conclusions miR-124-3p regulates keratinocyte activity via STAT3 in response to IL-17A stimulation. The ectopic expression of miR-124-3p in psoriatic skin reduces IL-17A-induced inflammation and inhibits the STAT3 pathway, thus alleviating the symptoms of psoriasis. The findings of this study suggest that exosomes can be used to therapeutically deliver miR-124-3p to keratinocytes and psoriatic lesions, which may provide novel insight for psoriasis treatment.