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

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eMediNexus    13 January 2023

The present study investigated the effect of azelaic acid on psoriasis based on the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway.

 

It downloaded Psoriasis gene expression data from the GEO database for differential expression analysis to identify differentially expressed genes (DEGs). The study performed KEGG and GSEA analyses to identify important signaling pathways that may be implicated in psoriasis progression for subsequent validation. It randomized thirty-six C57BL/6 mice aged eight weeks old into the blank control group, negative control group, psoriasis model group, and azelaic acid treat group. It carried out hematoxylin-eosin (HE) staining to explore the effect of azelaic acid on the pathological damage of mice models of psoriasis in each group. The study divided the HaCaT cells cultured in vitro into a blank control group, negative control group (addition of azelaic acid), IL-17 group (20 ng/mL), and IL-17+azelaic acid group, with three replicates for each group. It used immunofluorescence assay and Western blotting to detect the protein expression of PI3K/AKT signaling pathway-related molecules.

 

The study observed-

 

  • DEGs to be significantly enriched in PI3K-AKT signaling pathway in KEGG analysis.
  • Upregulation of PI3K and MTOR signaling pathways in psoriasis, while down-regulation of the AUTOPHAGY signaling pathway, in GSEA analysis.
  • Azelaic acid significantly inhibited the local skin injury in mice caused by IMQ-induced psoriasis in HE staining.
  • Azelaic acid inhibited the expression of PI3K/AKT signaling pathway-related proteins phosphorylated (p)-PI3K, p-AKT, a p-mammalian target of rapamycin (mTOR), vascular endothelial growth factor (VEGF), cyclooxygenase-2 (COX-2), angiogenin-1 and hypoxia-inducible factor-1α (HIF-1α). 

 

This study shows that azelaic acid may stop the activation of the PI3K/AKT signaling pathway and angiogenesis, thus improving the symptoms of psoriasis.

 

Clin Cosmet Investig Dermatol. 2022 Nov 23;15:2523-2534. Doi: 10.2147/CCID.S389760. PMID: 36447569; PMCID: PMC9701457.

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