Adiponectin and psoriasis

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Adiponectin (APN) holds potential as an anti-psoriatic agent  targeting Aurora kinase A (AURKA) and Forkhead transcription factor 1 (FOXM1) for the gene-targeted therapies in psoriasis treatment.

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Introduction:
Psoriasis is a recurrent immune-mediated systemic disease. Adiponectin (APN), a key regulator of metabolism, is also known for its anti-inflammatory properties in several inflammatory disorders. The study aims to investigate the anti-inflammatory properties of APN on human immortalized keratinocyte cells (HaCaT) and to evaluate its therapeutic potential in an imiquimod (IMQ)-induced psoriasis mouse model.

Methods:
HaCaT cells were treated with 5, 10, or 20 μg/ml APN, and cell viability was assessed. A psoriasis-like cellular model was created by exposing HaCaT cells to TNF-α (50 ng/ml) for a duration of 24 h. Apoptosis was analyzed using flow cytometry, and the secretion of inflammatory cytokines was measured through enzyme-linked immunosorbent assay (ELISA). Real-time quantitative polymerase chain reaction (RT-qPCR) was used to measure the mRNA expression levels of AdipoR1, AdipoR2, and T-cadherin(T-cad). Aurora kinase A (AURKA) and Forkhead transcription factor 1 (FOXM1) were analyzed using Western blotting (WB) and RT-qPCR. The anti-psoriatic effect of APN was also evaluated in IMQ-induced psoriatic dermatitis. Additionally, ELISA and WB were used to assess cytokines and key signaling proteins in mouse skin tissues.

Results:
APN significantly inhibited the proliferation of HaCaT cells and enhanced their apoptosis. Additionally, it decreased the production of interleukin (IL)-1β, IL-8, and IL-6. APN upregulated AdipoR1 and AdipoR2 mRNA levels while downregulating the mRNA and protein levels of T-cad. Mechanistically, APN mitigated the inflammatory response in keratinocytes by suppressing the TNF-α-induced upregulation of AURKA and FOXM1. This mechanism was substantiated in vivo, where APN treatment alleviated IMQ-induced psoriatic dermatitis in mice, concurrently reducing levels of IL-1β, CXCL2 and IL-6, and modulating the expression of AdipoR1, AdipoR2, AURKA, and FOXM1 in mouse skin.

Conclusion:
Our findings suggest that APN inhibits keratinocyte hyperproliferation and suppresses inflammation in TNF-α-induced keratinocytes. Moreover, APN treatment attenuates IMQ-induced psoriatic dermatitis in mice, supporting its potential as a therapeutic approach for psoriasis.

Source: onlinelibrary.wiley.com

*Funding: Youth Program of the Shanghai Municipal Health Commission. Youth Fund of Gongli Hospital, Shanghai Pudong New Area. Characteristic Diseases Discipline Construction Plan of the Pudong New Area Health System.