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논문분류	춘계학술대회 초록집
제목	New Biomarker for DKD: Urinary EV
저자	Dongsic Choi
출판정보	2024; 2024(1):
키워드
초록	Chronic kidney disease (CKD) is the gradual loss of kidney functionality mainly caused by diabetes mellitus or IgA nephropathy. Classically, CKD diagnosis by renal biopsy which is clinically very accurate but impractical in early diagnosis. Clinical indicators such as estimated glomerular filtration rate or albumin to creatinine ratio from urine biopsy are widely used for the kidney dysfunctionality but these values are not very specific and sensitive to discriminate the diverse types of CKD such as diabetic kidney disease (DKD). Recently, urinary extracellular vesicles (uEVs), 30-150 nm sized lipid bilayer vehicle, are considered to represent the pathophysiological status in urinary system. Although uEVs are effective biomarker source, their unique signature from EVs derived from other tissues or biological fluids is not well addressed. We applied the combination of concentration, SEC, and ultracentrifuge for the high purity EV isolation. In-gel digestion and LC-MS/MS by Orbitrap Eclipse Tribrid Mass Spectrometer were conducted to identify reliable EV proteomes. Total 1233, 1288, 1516, and 2728 proteins were identified in EVs derived from urine, CSF, colorectal cancer tissue, and caco-2 cell culture medium, respectively. Gene Ontology analyses showed the majority of identified proteins were related in membrane and cytosol rather than other cellular organelles implying our established EV isolation method equally applied in any EVs in diverse biological fluids. Impressively, some EV proteins differentially exist in specific biological fluids: urinary tract and kidney tissue proteins in urine, coagulation proteins in CSF, and epithelial cell proteins in colorectal cancer tissue. Especially, complements and inflammatory-related proteins were enriched in uEVs and validated in DKD patient cohorts. Our universal isolation method could provide the solid technical approaches for the EV proteomics in diverse biological fluids. These biomarkers could be applicable in high-sensitivity detection in DKD for the early diagnosis to monitor the pathophysiological status in urinary system.
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