The paeonol target gene autophagy-related 5 has a potential therapeutic value in psoriasis treatment

BACKGROUND: Paeonol is a potent therapy for psoriasis. This study aimed to screen out paeonol-targeted genes in psoriasis and validate the potential of using paeonol for the management of psoriasis. METHODS: Microarray datasets were obtained from the Gene Expression Omnibus. The differentially expressed genes (DEGs) in the lesional skin samples and the overlapping genes between DEGs and paeonol- and psoriasis-related genes were defined as potential targets for psoriasis. After being treated with si-ATG5 and pc-ATG5, human HaCaT cells were treated with 100 ng/ml IL-22 and 10 ng/ml TNF-α with and without paeonol. Cell proliferation, apoptosis, and expression of interleukin (IL)-6, IL-1β, Beclin 1, ATG5, and p62 in HaCaT cells were determined using ESLIA, PCR, and Western blot analysis. RESULTS: A total of 779 DEGs were identified in the lesional skin samples compared with the non-lesional tissues. The autophagy-related 5 (ATG5) gene was the only gene that overlapped between the DEGs and genes related to paeonol and psoriasis. Cell proliferation, inflammatory cytokines (IL-6 and IL-1β), and ATG5 expression were increased in IL-22/TNF-α-stimulated HaCaT (model) cells compared with control. Paeonol treatment rescued all changes. si-ATG5 transfection increased inflammation and apoptosis in model cells compared with controls. pc-ATG5 prevented IL-22/TNF-α-induced changes in HaCaT cells. Also, si-ATG5 decreased p62 and Beclin 1 proteins, while pc-ATG5 increased them both. CONCLUSIONS: ATG5-dependent autophagy plays a crucial role in psoriasis. The ATG5 gene might be a therapeutic target for the management of in vitro psoriasis.