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Comparative Proteomic Analysis Reveals Altered Ciliary Proteins in Sickle Cell Disease

delete2025-05-15
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PRE
AI
A
Ashraf M. Mohieldin *
M
Madison Spencer
C
Carter Bernal
W
Wala B. Fadol
A
Ankan Gupta
K
Karthikeyan Thirugnanam
C
Claire Delahunty
F
Francisco Núñez
A
Amy Pan
A
Amanda M. Brandow
S
Sean P. Palecek
K
Kevin R. Rarick
R
Ramani Ramchandran
R
Rahima Zennadi
J
John R. Yates
DOI：10.1021/acs.jproteome.5c00168delete
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Abstract

Abstract

En 中文
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/cm2 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.
Keywords:
sickle cell disease
sicklecell trait
redblood cells
vascular damage
primary cilia
extracellular vesicles
proteomics
diagnosticbiomarker

Journal

Journal of Proteome Research cover
Journal of Proteome Research
IF:
3.6
Papers:
9.3K
Citations:
2.3W

Organization

No organization information available