Proteomic analyses of urinary exosomes identify heparanase, cathepsin C, 2-macroglobulin and sarcoplasmic endoplasmic Ca2+ ATPase-3 (SERCA3) as potential biomarkers for early diagnosis of sickle nephropathy

ABSTRACT: Sickle cell disease-induced nephropathy (SCN) is a leading cause of morbidity and mortality in sickle cell disease (SCD). Early intervention is crucial for mitigating its effects. However, current diagnostic methods rely on non-specific tests and may not detect SCN until renal damage has become irreversible. Therefore, specific biomarkers for early diagnosis of SCN are urgently needed. Urinary exosomes, membrane-bound vesicles secreted by renal podocytes and epithelial cells, contain both common and cell type-specific membrane and cytosolic proteins, reflecting the physiological and pathophysiological states of the kidney. Using proteomics, we analyzed the proteomes of urinary exosomes from 5 humanized SCD mice (Townes model) at 2 months (without albuminuria) and 4 months (with albuminuria) of age. We found that excretion of 166 proteins was significantly increased and 174 proteins was significantly decreased in the exosomes when mice developed albuminuria. Based on the relevance to SCD, chronic kidney disease and Western confirmation in mice, we analyzed protein abundance of heparanase, cathepsin C, α2-macroglobulin and SERCA3 in the urinary exosomes and urine of 18 SCD patients without albuminuria and 12 patients with albuminuria using Western analyses. We found that increased excretion of these proteins in the urinary exosomes and urine correlated with albuminuria in the patients. Furthermore, excretion of heparanase, cathepsin C, and α2-macroglobulin in the urinary exosomes correlated with their excretion in the urine and urinary albumin creatinine ratio. In conclusion, our results suggest that heparanase, cathepsin C, α2-macroglobulin and SERCA3 could serve as specific and reliable biomarkers for early detection of SCN.

ORGANISM(S): Mus Musculus (mouse)

SUBMITTER: Xiaoming Zhou 

PROVIDER: PXD043401 | JPOST Repository | Wed Feb 07 00:00:00 GMT 2024

REPOSITORIES: jPOST