ROBO4 Deletion Ameliorates PAF-Mediated Skin Inflammation by Regulating the mRNA Translation Efficiency of LPCAT1/LPCAT2 and the Expression of PAF Receptor

The study from 2020 found that deleting the Roundabout 4 (ROBO4) gene in mice led to reduced skin inflammation and hair loss by interfering with the platelet-activating factor (PAF) pathway. This was achieved by decreasing the protein expression of PAF synthetic enzymes LPCAT1/LPCAT2 in macrophages, reducing the expression of the PAF receptor, and increasing the expression of platelet-activating factor acetylhydrolase (PAFAH) in serum. The deletion also resulted in a decrease in genes related to oxidative phosphorylation and ribosome expression in macrophages, as well as a reduction in ATP concentration. Furthermore, the study showed that ROBO4 deletion suppressed inflammation induced by lipopolysaccharide (LPS), as indicated by reduced IL-6 expression and phosphorylation of signaling molecules. The study involved more than 24 neonates in each group across F1 and F2 generations, suggesting that the findings are robust. The conclusion is that ROBO4 deletion may be a potential therapeutic target for treating PAF-mediated skin inflammation and hair loss.