SLC27A2as a molecular marker of impaired epithelium in chronic rhinosinusitis with nasal polyps

Abstract

ABSTRACTBackgroundChronic rhinosinusitis with nasal polyps (CRSwNP) is a complex disease characterized by multiple inflammatory endotypes. Although recent progress has been made in endotype-based classification, developing tailored therapeutic strategies for CRSwNP remains challenging. This study aimed to optimize therapeutic outcomes in CRSwNP by identifying potential molecular markers.MethodsWe utilized an integrated approach that combined bulk and single-cell RNA sequencing (scRNA-seq) to delineate the molecular signatures inherent to the cellular components of nasal polyp (NP) tissue. The levels of C11-BODIPY (as a marker of lipid peroxidation) andSLC27A2/FATP2 were assessed using quantitative PCR and immunofluorescence (IF) staining. The effects of lipofermata, a FATP2 inhibitor, were examined in air-liquid interface (ALI) cultured epithelial cells derived from CRSwNP patients and healthy controls.ResultsDeconvolution analysis of NP tissue revealed an upregulation of genes associated with lipid metabolism in the NP epithelium. In CRSwNP patients, we observed a significant increase in lipid peroxidation andSLC27A2/FATP2 expression in the NP epithelium. A marked expression of genes critical to metabolic pathways involved in lipid peroxidation was identified inSLC27A2-positive epithelial cells. Additionally, FATP2 and lipid peroxidation staining patterns exhibited a positive correlation in their respective % Area levels. ElevatedSLC27A2expression was associated with disease pathogenesis and correlated with disease severity. Treatment with lipofermata resulted in decreased mRNA levels ofALOX15, a key mediator of inflammation and lipid peroxidation, andFOXJ1, a marker of abnormal ciliogenesis.ConclusionElevatedSLC27A2expression in the NP epithelium correlates with the severity of CRSwNP, highlighting its potential as a therapeutic target for managing advanced CRSwNP cases.