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Isocitrate dehydrogenase 1 upregulation in urinary extracellular vesicles from proximal tubules of type 2 diabetic rats.
- Source :
-
FASEB journal : official publication of the Federation of American Societies for Experimental Biology [FASEB J] 2024 May 31; Vol. 38 (10), pp. e23688. - Publication Year :
- 2024
-
Abstract
- Diabetic nephropathy (DN) is a major cause of chronic kidney disease. Microalbuminuria is currently the most common non-invasive biomarker for the early diagnosis of DN. However, renal structural damage may have advanced when albuminuria is detected. In this study, we sought biomarkers for early DN diagnosis through proteomic analysis of urinary extracellular vesicles (uEVs) from type 2 diabetic model rats and normal controls. Isocitrate dehydrogenase 1 (IDH1) was significantly increased in uEVs from diabetic model rats at the early stage despite minimal differences in albuminuria between the groups. Calorie restriction significantly suppressed the increase in IDH1 in uEVs and 24-hour urinary albumin excretion, suggesting that the increase in IDH1 in uEVs was associated with the progression of DN. Additionally, we investigated the origin of IDH1-containing uEVs based on their surface sugar chains. Lectin affinity enrichment and immunohistochemical staining showed that IDH1-containing uEVs were derived from proximal tubules. These findings suggest that the increase in IDH1 in uEVs reflects pathophysiological alterations in the proximal tubules and that IDH1 in uEVs may serve as a potential biomarker of DN in the proximal tubules.<br /> (© 2024 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.)
- Subjects :
- Animals
Rats
Biomarkers urine
Biomarkers metabolism
Rats, Sprague-Dawley
Up-Regulation
Diabetes Mellitus, Experimental metabolism
Diabetes Mellitus, Experimental urine
Diabetes Mellitus, Type 2 urine
Diabetes Mellitus, Type 2 metabolism
Diabetic Nephropathies urine
Diabetic Nephropathies metabolism
Diabetic Nephropathies pathology
Extracellular Vesicles metabolism
Isocitrate Dehydrogenase metabolism
Isocitrate Dehydrogenase genetics
Kidney Tubules, Proximal metabolism
Kidney Tubules, Proximal pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1530-6860
- Volume :
- 38
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- FASEB journal : official publication of the Federation of American Societies for Experimental Biology
- Publication Type :
- Academic Journal
- Accession number :
- 38780519
- Full Text :
- https://doi.org/10.1096/fj.202400371R