Effect of Azelaic Acid on Psoriasis Progression Investigated Based on Phosphatidylinositol 3-Kinase (PI3K)/Protein Kinase B (AKT) Signaling Pathway

Abstract

Objective To probe into the effect of azelaic acid on psoriasis based on the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway. Methods Psoriasis gene expression data were downloaded from the GEO database for differential expression analysis to identify differentially expressed genes (DEGs). KEGG and GSEA analyses were performed to identify important signaling pathways that may be involved in psoriasis progression for subsequent validation. Thirty-six C57BL/6 mice aged 8 weeks old were randomly assigned into the blank control group (n = 9), negative control group (n = 9), psoriasis model group (n = 9), and azelaic acid treat group (n = 9). Mice models of psoriasis were prepared with imiquimod (IMQ) in the latter two groups, and azelaic acid ointment was applied in azelaic acid treat group. Then, hematoxylin-eosin (HE) staining was carried out to detect the effect of azelaic acid on the pathological damage of mice models of psoriasis in each group. HaCaT cells cultured in vitro were divided into blank control group, negative control group (addition of azelaic acid), IL-17 group (20 ng/mL) and IL-17+azelaic acid group, with 3 replicates for each group. Immunofluorescence assay and Western blotting were used to detect the protein expression of PI3K/AKT signaling pathway related molecules. Results KEGG analysis showed that DEGs were significantly enriched in PI3K-AKT signaling pathway. GSEA analysis showed that PI3K and MTOR signaling pathways were up-regulated in psoriasis, while AUTOPHAGY signaling pathway was down-regulated. HE staining showed that azelaic acid could significantly inhibit the local skin injury in mice caused by IMQ-induced psoriasis. Moreover, azelaic acid can inhibit the expression of PI3K/AKT signaling pathway related proteins phosphorylated (p)-PI3K, p-AKT, p-mammalian target of rapamycin (mTOR), vascular endothelial growth factor (VEGF), cyclooxygenase-2 (COX-2), angiogenin-1 and hypoxia-inducible factor-1α (HIF-1α). These results imply that azelaic acid may inhibit the activation of PI3K/AKT signaling pathway and angiogenesis, thereby improving the symptoms of psoriasis. Conclusion Azelaic acid may inhibit the activation of PI3K/AKT signaling pathway and angiogenesis, thereby improving the symptoms of psoriasis.