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PMID: 18509321 Published · ppublish English Journal Article Research Support, N.I.H., Intramural

Urinary exosomal transcription factors, a new class of biomarkers for renal disease.

Kidney international ·Vol. 74 ·No. 5 ·2008-09-00 ·Pages 613-21

Zhou H, Cheruvanky A, Hu X, Matsumoto T, Hiramatsu N, Cho ME, Berger A, Leelahavanichkul A, Doi K, Chawla LS, Illei GG, Kopp JB, Balow JE, Austin HA, Yuen PS, Star RA

Abstract

Urinary exosomes are excreted from all nephron segments and constitute a rich source of intracellular kidney injury biomarkers. To study whether they contain transcription factors, we collected urine from two acute kidney injury models (cisplatin or ischemia-reperfusion), two podocyte injury models (puromycin-treated rats or podocin-Vpr transgenic mice) and from patients with focal segmental glomerulosclerosis, acute kidney injury and matched controls. Exosomes were isolated by differential centrifugation and found to contain activating transcription factor 3 (ATF3) and Wilms Tumor 1 (WT-1) proteins detected by Western blot. These factors were found in the concentrated exosomal fraction, but not in whole urine. ATF3 was continuously present in urine exosomes of the rat models following acute injury at times earlier than the increase in serum creatinine. ATF3 was found in exosomes isolated from patients with acute kidney injury but not from patients with chronic kidney disease or controls. Urinary WT-1 was present in animal models before significant glomerular sclerosis and in 9/10 patients with focal segmental glomerulosclerosis but not in 8 controls. Our findings suggest that transcription factor ATF3 may provide a novel renal tubular cell biomarker for acute kidney injury while WT-1 may detect early podocyte injury. Measurement of urinary exosomal transcription factors may offer insight into cellular regulatory pathways.

MeSH Terms
Activating Transcription Factor 3/urine Acute Kidney Injury/chemically induced,urine Adult Aged Animals Biomarkers/urine Case-Control Studies Cisplatin/toxicity Gene Products, vpr/genetics Glomerulosclerosis, Focal Segmental/urine Humans Intracellular Signaling Peptides and Proteins/genetics Kidney/injuries Kidney Diseases/urine Male Membrane Proteins/genetics Mice Mice, Transgenic Middle Aged Podocytes/drug effects,pathology,physiology Rats Rats, Sprague-Dawley Reperfusion Injury/urine Transcription Factors/urine WT1 Proteins/urine
Chemicals
Activating Transcription Factor 3 Biomarkers Gene Products, vpr Intracellular Signaling Peptides and Proteins Membrane Proteins NPHS2 protein Transcription Factors WT1 Proteins Cisplatin
Authors & Affiliations
16 authors, click to expand affiliations / ORCID
Zhou Hua
Renal Diagnostics and Therapeutics Unit, National Institutes of Health, Bethesda, Maryland, USA.
Cheruvanky Anita
Hu Xuzhen
Matsumoto Takayuki
Hiramatsu Noriyuki
Cho Monique E
Berger Alexandra
Leelahavanichkul Asada
Doi Kent
Chawla Lakhmir S
Illei Gabor G
Kopp Jeffrey B
Balow James E
Austin Howard A
Yuen Peter S T
Star Robert A
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Article Info
Journal
Kidney international
Abbr.
Kidney Int
ISSN
1523-1755
DOI
10.1038/ki.2008.206
Published
2008-09-00
Epub
2008-00-28
Pages
613-21
Language
English
Region
United States
NLM ID
0323470
PMCID
PMC2562924
Subset
IM
Grants
Intramural NIH HHS · Z01 DK043400-08 · United States
External Links
PubMed source DOI: 10.1038/ki.2008.206 PMC Full Text View journal details
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