MiR-125a-3p alleviates hyperproliferation of keratinocytes and psoriasis-like inflammation by targeting TLR4/NF-κB pathway.

INTRODUCTION

Psoriasis is a chronic auto-inflammatory dermatosis characterized by hyperproliferation of keratinocytes. Emerging evidence has validated the dysregulated expression of microRNAs (miRNAs/miRs) in psoriasis patients.

AIM: To probe into the role and precise mechanism of miR-125a-3p in HaCaT cells and imiquimod (IMQ)-stimulated psoriasis-like mice.

MATERIAL AND

METHODS

In M5-treated HaCaT cells and IMQ-stimulated psoriasis-like mice, real-time quantitative polymerase chain reaction and western blot analysis were performed for detecting gene expression. Hematoxylin and eosin staining was used to evaluate pathological morphology of IMQ-induced psoriasis skin. The proliferation of keratinocytes was assessed using Cell Counting Kit-8 assay and Ki67 positive staining. The combination between miR-125a-3p and Toll-like receptor 4 (TLR4) was confirmed by luciferase reporter assay.

RESULTS

Our study showed reduced miR-125a-3p expression in psoriasis patients, psoriasis-like inflammatory cell models, and IMQ-generated psoriasis-like mouse models. MiR-125a-3p repressed the activity of keratinocytes in vitro by suppressing cell proliferation, inhibiting the production of psoriasis-related genes and inflammatory genes, and inactivating the NF-κB and interleukin (IL)-1β pathways. Notably, the psoriasis-like inflammation was repressed by intradermal injection of agomiR-125a-3p in psoriatic mouse models in vivo. Mechanically, miR-125a-3p targeted and negatively regulated TLR4. Furthermore, the elevated expression of TLR4 reversed the influences of miR-125a-3p mimics on HaCaT cells.

CONCLUSIONS

Upregulation of miR-125a-3p protects keratinocytes against hyperproliferation and inflammatory damage by inhibiting TLR4, suggesting that the miR-125a-3p/TLR4 axis might become a novel target for the prevention of psoriasis.