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Comparative Proteomic Analysis Reveals Altered Ciliary Proteins in Sickle Cell Disease

Year: 2025

Type: article

Abstract: Sickle cell disease (SCD) is an inherited hemoglobinopathy characterized by sickle-shaped red blood cells (RBCs). Primary cilia are mechanosensory organelles and are projected in the lumen of blood vessels to detect blood flow. We previously reported that interaction between microvasculature endothelial cells and sickled RBCs resulted in altered blood flow that can elevate reactive oxygen species, leading to increased deciliation in SCD patients. However, the impact of deciliation mediated by sickled RBCs in the context of the ciliary protein profiles remains unclear. Here, we investigated cell-cilia stability under different physiological shear-stress magnitudes and examined cilia protein profiles in SCD, utilizing mouse models and human participants. Our results demonstrate that subjecting endothelial cilia to sickled RBCs at 5.0 dyn/cm 2 led to significant deciliation events. The proteomic and bioinformatic analyses showed different ciliary protein profiles, distinct signaling pathways, and unique post-translational modification processes in the SCD mouse model. Consistent with the SCD mouse model results, our translational studies validated the enrichment of specific proteins, including Transferrin Receptor-1 (TfR1), Glyceraldehyde-3-Phosphate-Dehydrogenase (GAPDH), and ADP Ribosylation Factor Like GTPase-13B (ARL13B) in SCD patients. These findings underscore the clinical relevance of cilia in SCD and suggest that ciliary proteins are potential biomarkers for assessing vascular damage.

Source: Journal of Proteome Research

DOI: 10.1021/acs.jproteome.5c00168