Downregulation of Mitophagy, Complex I Biogenesis, and Signaling by ROBO Receptors-Implications for Psoriasis...

The pathogenesis of psoriasis is complex and many specific immunopathogenic mechanisms still remain unclear. Our goal was to identify novel pathways involved in the pathogenesis of psoriasis by analyzing differentially expressed genes, and to conduct pathway and cluster analysis by comparing lesional and non-lesional skin with healthy controls. Accordingly, 2 mm punch biopsies were taken from lesional elbow skin and non-affected adjacent skin of 23 patients with plaque-type psoriasis and from the elbow skin of 25 healthy controls. Differentially expressed genes were analyzed through RNA sequencing, and gene set enrichment analysis was used to analyze biological pathways. Our results showed downregulation of the pathway clusters "Mitophagy" and "Respiratory Electron Transport" when comparing both lesional and non-lesional skin to control skin. The pathway "Signaling by ROBO receptors" was downregulated in all three comparisons. Conversely, pathways relating to SUMOylation were upregulated when comparing lesional skin to both non-lesional and control skin, and those relating to the synthesis of PIPs at the early endosome membrane were found to be upregulated in lesional skin compared to control skin. The dysregulation of pathways relating to mitophagy (involved in the removal of damaged mitochondria), complex I biogenesis (a component of the mitochondrial respiratory chain), signaling by ROBO receptors (important for cell migration), and the synthesis of PIPs at the early endosome membrane (with a pivotal role in endocytic pathways and autophagy) suggests their potential role in psoriasis. Further research into the mechanisms of these dysregulated pathways, along with confirmation of protein expression levels, is necessary to validate their roles in psoriasis pathogenesis.