Comparative Proteomic Analysis Reveals Altered Ciliary Proteins in Sickle Cell Disease

Area of Science:

• Cell biology
• Hematology
• Vascular biology

Background:

• Sickle cell disease (SCD) involves abnormal red blood cells (RBCs) impacting blood flow.
• Primary cilia in endothelial cells detect blood flow and are affected by sickled RBCs, leading to deciliation.
• The specific impact of sickled RBCs on ciliary protein profiles in SCD is not well understood.

Purpose of the Study:

• To investigate endothelial cell-cilia stability under varying shear stress in SCD.
• To analyze ciliary protein profiles in mouse models and human participants with SCD.
• To identify potential ciliary biomarkers for vascular damage in SCD.

Main Methods:

• Utilized mouse models and human participants with SCD.
• Subjected endothelial cilia to sickled RBCs under controlled shear stress (5.0 dyn/cm²).
• Performed proteomic and bioinformatic analyses of ciliary proteins and post-translational modifications.

Main Results:

• Significant deciliation events occurred when endothelial cilia were exposed to sickled RBCs at 5.0 dyn/cm².
• SCD mouse models exhibited distinct ciliary protein profiles, signaling pathways, and post-translational modifications.
• Translational studies confirmed enrichment of Transferrin Receptor-1 (TfR1), GAPDH, and ARL13B in SCD patients.

Conclusions:

• Endothelial cilia stability is compromised by sickled RBCs in SCD.
• Ciliary protein profiles differ significantly in SCD, indicating altered cellular processes.
• Specific ciliary proteins like TfR1, GAPDH, and ARL13B are potential biomarkers for vascular damage in SCD.