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Open Access 01-12-2021 | Diabetic Nephropathy | Research

Urinary small extracellular vesicles derived CCL21 mRNA as biomarker linked with pathogenesis for diabetic nephropathy

Authors: Ye Feng, Xin Zhong, Hai-Feng Ni, Cui Wang, Tao-Tao Tang, Li-Ting Wang, Kai-Yun Song, Ri-Ning Tang, Hong Liu, Bi-Cheng Liu, Lin-Li Lv

Published in: Journal of Translational Medicine | Issue 1/2021

Abstract

Background

Diabetic nephropathy (DN) is a leading cause of renal failure, whereas the effective and early diagnostic biomarkers are still lacking.

Methods

Fourteen cytokines and chemokines mRNA were detected in urinary extracellular vesicles (EVs) from the screening cohort including 4 healthy controls (HC), 4 diabetes mellitus (DM) and 4 biopsy-proven DN patients, and was validated in another 16 HC and 15 DM and 28 DN patients. Correlation analysis was performed between the candidate biomarkers and clinic parameters as well as kidney histological changes. The findings were also confirmed in DN rat model with single injection of STZ.

Results

The number of small EVs secreted in urine was increased in DN patients compared to DM patients and healthy controls, with expression of AQP1 (a marker of proximal tubules) and AQP2 (a marker of distal/collecting tubules). Small EVs derived CCL21 mRNA increased significantly in DN patients and correlated with level of proteinuria and eGFR. Interestingly, elevated CCL21 mRNA from urine small EVs was observed in DN patients with normal renal function and could discriminate early DN patients from DM more efficiently compared to eGFR and proteinuria. CCL21 also showed an accurate diagnostic ability in distinguishing incipient from overt DN. Histologically, CCL21 mRNA expression increased progressively with the deterioration of tubulointerstitial inflammation and showed the highest level in nodular sclerosis group (class III) in DN patients. Remarkable infiltration of CD3 positive T cells including both CD4 and CD8 positive T cell population were observed in DN patients with high-CCL21 expression. Besides, accumulation of CD3 positive T cells correlated with level of urinary small EVs derived CCL21 and co-localized with CCL21 in the tubulointerstitium in DN patients. Finally, the correlation of CCL21 expression in renal cortex and urinary small EVs was confirmed in STZ-induced DN rat model.

Conclusions

Urinary small EVs derived CCL21 mRNA may serve as early biomarker for identifying DN linked with pathogenesis. CCL21 mRNA mediated T cell infiltration may constitute the key mechanism of chronic inflammation in DN.

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Title: Urinary small extracellular vesicles derived CCL21 mRNA as biomarker linked with pathogenesis for diabetic nephropathy
Authors: Ye Feng
Xin Zhong
Hai-Feng Ni
Cui Wang
Tao-Tao Tang
Li-Ting Wang
Kai-Yun Song
Ri-Ning Tang
Hong Liu
Bi-Cheng Liu
Lin-Li Lv
Publication date: 01-12-2021
Publisher: BioMed Central
Keywords: Diabetic Nephropathy
Biomarkers
Published in: Journal of Translational Medicine / Issue 1/2021
Electronic ISSN: 1479-5876
DOI: https://doi.org/10.1186/s12967-021-03030-x

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