VDAC1 and RhoA in Plasma Exosomes Influence the Severity of Adolescent Idiopathic Scoliosis

Background: Adolescent idiopathic scoliosis (AIS) is the most common spine deformity, but biomarkers for its condition are lacking. Rhodopsin A (RhoA) and voltage-dependent anion-selective channel 1 (VDAC1) in plasma exosomes were defined as differentially expressed proteins between AIS patients and healthy controls. The purpose of this study was to assess exosomes as biomarkers for the occurrence and progression of AIS.

Methods:We recruited 10 AIS patients and 8 healthy controls to detect expressed proteins from plasma by liquid chromatography coupled to tandem mass spectrometry. Plasma samples were analyzed by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). Pathway analysis identified that the VDAC1 and RhoA proteins were alterations expressed in the AIS patients, with the most different alteration was found in extracellular exosomes. Ultracentrifugation was carried out to isolate exosomes from plasma. Verification of the most differentially expressed protein was accessed by Western blot analysis and bioinformatics analysis was performed to predict the pathway of it.

Results: 42 of significantly differentially expressed proteins were found in all subjects, and 17 proteins had significant difference. The differentially expressed proteins were enriched in plasma exosomes, and some proteins, such as FN1, were upregulated and others, such as VDAC1, RhoA and AHNAK, were downregulated in the AIS patients. Furthermore, ultracentrifugation was carried out to isolate exosomes from plasma, and RhoA and VDAC1 proteins in plasma exosomes were verified to downregulate by western blot. KEGG signaling pathways were used to predict potential pathways involved in the RhoA and VDAC1 proteins in the AIS patients. We found that the RhoA protein influences AIS probably through the chemokine signaling pathway, platelet activation and cAMP signaling pathway, and the VDAC1 protein is a key factor that participates in the necroptosis pathway, acting on the development of AIS.

Conclusions: Consequently, this study mapped a profile of plasma protein, found the differentially expressed protein in AIS, which indicating that plasma exosomes, as a novel biomarker with high specificity, could be associated with the severity of AIS.