Differential Expression of Endocannabinoid Receptors in Lesional and Non-Lesional Skin of Psoriasis Patients: Insights Into Pathogenesis and Potential Therapeutic Targets

Background: Psoriasis is a chronic, immune-mediated inflammatory skin disease with a complex etiology involving genetics, environmental triggers, and immune dysregulation. Research suggests that the endocannabinoid system (ECS) is involved in inflammation and skin homeostasis, prompting interest in its involvement in the pathogenesis of psoriasis.Objectives: This study was designed to investigate the expression of cannabinoid receptors and signaling channels in psoriatic-affected tissue (lesional), unaffected tissue (non-lesional), and healthy control subjects.Methods: Data were extracted using bulk RNA sequencing data from the Gene Expression Omnibus public database. Differential gene expression analysis was performed to determine changes in cannabinoid receptor expression between psoriatic lesional skin, non-lesional skin, and healthy controls.Results: We found that in psoriatic lesional skin, GPR12, PPARG, TRPV4, PPARA, and HTR1A were significantly downregulated, while CNR2, TRPA1, TRPV3, PPARD, GPR18, ADORA2A, HTR3B, and HTR3A were notably upregulated compared to healthy controls. In addition, TRPV4, PPARG, PPARA, and GPR12 were markedly downregulated in psoriatic lesional skin compared to non-lesional skin, while PPARD, HTR3A, HTR3B, GPR18, TRPV3, TRPA1, CNR2, and ADORA2A showed significant upregulation. There were no significantly upregulated or downregulated endocannabinoid genes in the non-lesional to healthy control analysis.Conclusions: These findings provide new insights into the role of the ECS in psoriasis pathogenesis and highlight potential targets for further research or novel therapeutic interventions.