MicroRNA-29c in urinary exosome/microvesicle as a biomarker of renal fibrosis.
Micro (mi)RNAs are frequently dysregulated in the development of renal fibrosis. Exosomes are small membrane vesicles that could be isolated from urine secreted from all nephron segments. Here we sought to observe for the first time whether miRNA in urine exosome could serve as a potential biomarker of renal fibrosis. Urine samples were collected from 32 chronic kidney disease (CKD) patients who underwent kidney biopsy and 7 controls. Exosome was isolated and confirmed by immunogold staining of exosome marker. Members of miR-29, miR-200, and RNU6B as endogenous control were detected by RT quantitative PCR. Electronic microscopy verified a typical shape of exosome with average size of 65.1 nm and labeled it with anti-CD9 and anti-aquaporin 2 antibody. Members of miR-29 and miR-200 are readily measured with reduced levels compared with controls (P < 0.05) and can robustly distinguish CKD from controls [area under the curve (AUC) varied from 0.902 to 1 by receiver operating characteristics analysis]. miR-29c correlated with both estimated glomerular filtration rate (r = 0.362; P < 0.05) and degree of tubulointerstitial fibrosis (r = -0.359; P < 0.05) for CKD patients. Moreover, miRNA in exosome was decreased in mild fibrosis group compared with moderated to severe group. miR-29a and miR-29c could predict degree of tubulointerstitial fibrosis with AUC of 0.883 and 0.738 (P < 0.05). The sensitivity and specificity for distinguishing mild from moderate to severe fibrosis were 93.8 and 81.3% with the use of miR-29a and 68.8 and 81.3% for miR-29c. Overall, miR-29c in urinary exosome correlates with both renal function and degree of histological fibrosis, suggesting it as a novel, noninvasive marker for renal fibrosis.
Institute of Nephrology, Zhongda Hospital School of Medicine, Southeast Univ., No. 87 Ding JiaQiao Rd., Nanjing, China 210009. liubc64@163.com.
Lin-Li
LL
Lv
Yu-Han
YH
Cao
Hai-Feng
HF
Ni
Min
M
Xu
Dan
D
Liu
Hong
H
Liu
Ping-Sheng
PS
Chen
Bi-Cheng
BC
Liu
D000328:Adult; D015415:Biomarkers / Q000652:urine; D016022:Case-Control Studies; D055354:Exosomes / Q000235:genetics* / Q000473:pathology; D005260:Female; D005355:Fibrosis / Q000235:genetics / Q000473:pathology / Q000652:urine; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000652:urine*; D008875:Middle Aged; D009400:Nephrosclerosis / Q000235:genetics / Q000473:pathology / Q000652:urine*; D051436:Renal Insufficiency, Chronic / Q000235:genetics / Q000473:pathology / Q000652:urine*
D015415:Biomarkers; C533896:MIRN200 microRNA, human; C532045:MIRN29a microRNA, human; D035683:MicroRNAs
biomarker; exosome; microrna; tubulointerstitial fibrosis; urine