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Urinary Exosomes and Exosomal CCL2 mRNA as Biomarkers of Active Histologic Injury in IgA Nephropathy.

Publication ,  Journal Article
Feng, Y; Lv, L-L; Wu, W-J; Li, Z-L; Chen, J; Ni, H-F; Zhou, L-T; Tang, T-T; Wang, F-M; Wang, B; Chen, P-S; Crowley, SD; Liu, B-C
Published in: Am J Pathol
November 2018

IgA nephropathy (IgAN) features variable renal pathology and a heterogeneous clinical course. Our aim was to search noninvasive biomarkers from urinary exosomes for IgAN patients; membrane nephropathy and minimal change disease were included as other glomerulopathy controls. Transmission electron microscopy and nanoparticle tracking analysis confirmed the size and morphology characteristic of urinary exosomes. Exosome markers (Alix and CD63) as well as renal cell markers [aquaporin 2 (AQP2) and nephrin] were detected, which indicate the renal origin of urinary exosomes. Exosome excretion was increased markedly in IgAN patients compared with controls and correlated with levels of proteinuria and tubular injury. More important, urinary exosome excretion correlated with greater histologic activity (mesangial hypercellularity, crescents, and endocapillary hypercellularity). Profiling of the inflammation-related mRNA revealed that exosomal chemokine (C-C motif) ligand 2 (CCL2) was up-regulated in IgAN patients. In a validation study, CCL2 was exclusively highly expressed in IgAN patients compared with healthy controls as well as minimal change disease and membrane nephropathy patients. Also, a correlation between exosomal CCL2 and estimated glomerular filtration rate levels was found in IgAN. Exosomal CCL2 was correlated with tubulointerstitial inflammation and C3 deposition. High CCL2 levels at the time of renal biopsy were associated with subsequent deterioration in renal function. Thus, urinary exosomes and exosomal CCL2 mRNA are promising biomarkers reflecting active renal histologic injury and renal function deterioration in IgAN.

Duke Scholars

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Published In

Am J Pathol

DOI

EISSN

1525-2191

Publication Date

November 2018

Volume

188

Issue

11

Start / End Page

2542 / 2552

Location

United States

Related Subject Headings

  • RNA, Messenger
  • Pathology
  • Nephritis, Interstitial
  • Male
  • Inflammation
  • Humans
  • Glomerulonephritis, IGA
  • Glomerular Filtration Rate
  • Female
  • Exosomes
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Feng, Y., Lv, L.-L., Wu, W.-J., Li, Z.-L., Chen, J., Ni, H.-F., … Liu, B.-C. (2018). Urinary Exosomes and Exosomal CCL2 mRNA as Biomarkers of Active Histologic Injury in IgA Nephropathy. Am J Pathol, 188(11), 2542–2552. https://doi.org/10.1016/j.ajpath.2018.07.017
Feng, Ye, Lin-Li Lv, Wei-Jun Wu, Zuo-Lin Li, Jun Chen, Hai-Feng Ni, Le-Ting Zhou, et al. “Urinary Exosomes and Exosomal CCL2 mRNA as Biomarkers of Active Histologic Injury in IgA Nephropathy.Am J Pathol 188, no. 11 (November 2018): 2542–52. https://doi.org/10.1016/j.ajpath.2018.07.017.
Feng Y, Lv L-L, Wu W-J, Li Z-L, Chen J, Ni H-F, et al. Urinary Exosomes and Exosomal CCL2 mRNA as Biomarkers of Active Histologic Injury in IgA Nephropathy. Am J Pathol. 2018 Nov;188(11):2542–52.
Feng, Ye, et al. “Urinary Exosomes and Exosomal CCL2 mRNA as Biomarkers of Active Histologic Injury in IgA Nephropathy.Am J Pathol, vol. 188, no. 11, Nov. 2018, pp. 2542–52. Pubmed, doi:10.1016/j.ajpath.2018.07.017.
Feng Y, Lv L-L, Wu W-J, Li Z-L, Chen J, Ni H-F, Zhou L-T, Tang T-T, Wang F-M, Wang B, Chen P-S, Crowley SD, Liu B-C. Urinary Exosomes and Exosomal CCL2 mRNA as Biomarkers of Active Histologic Injury in IgA Nephropathy. Am J Pathol. 2018 Nov;188(11):2542–2552.
Journal cover image

Published In

Am J Pathol

DOI

EISSN

1525-2191

Publication Date

November 2018

Volume

188

Issue

11

Start / End Page

2542 / 2552

Location

United States

Related Subject Headings

  • RNA, Messenger
  • Pathology
  • Nephritis, Interstitial
  • Male
  • Inflammation
  • Humans
  • Glomerulonephritis, IGA
  • Glomerular Filtration Rate
  • Female
  • Exosomes