PXD043401-1

PXD043401 is an original dataset announced via ProteomeXchange.

Title	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
Description	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.
HostingRepository	jPOST
AnnounceDate	2024-02-07
AnnouncementXML	Submission_2024-02-07_07:58:37.098.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD043401
ReviewLevel	Non peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Balamurugan Packialakshmi
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	S-carboxamidomethyl-L-cysteine; L-methionine sulfoxide
Instrument	LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2023-06-29 09:50:28	ID requested
⏵ 1	2024-02-07 07:58:37	announced
2	2024-03-07 10:23:38	announced	2024-03-08: Updated PubMed.

Dataset with its publication pending

submitter keyword: sickle cell disease, kidney, urine, albuminuria, humanized sickle cell disease mice.

Xiaoming Zhou
lab head
Balamurugan Packialakshmi
contact affiliation	USUHS
dataset submitter

jPOST dataset URI

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