Evidence map›Paper›PMID 34404433›Full record

ArticleJournal of translational medicine2021

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

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 and 1 more

Open access · goldAbstract read
In one paragraph

Article in Journal of translational medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed, 4 pooled it
2.1field-weighted citation impact, top 12% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

33 citing papers in PubMed, 4 syntheses or guidelines pooled it, 38 citations in OpenAlex.

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  18. Research progress on small extracellular vesicles in diabetic nephropathy.Frontiers in cell and developmental biology · 2025
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 1 institution in 1 country.

Ye FengInstitute of Nephrology, Zhongda Hospital, Southeast University School of Medicine, 87 Ding Jia Qiao Road, Nanjing, 210009, Jiangsu, China.
Xin ZhongInstitute of Nephrology, Zhongda Hospital, Southeast University School of Medicine, 87 Ding Jia Qiao Road, Nanjing, 210009, Jiangsu, China.
Hai-Feng NiInstitute of Nephrology, Zhongda Hospital, Southeast University School of Medicine, 87 Ding Jia Qiao Road, Nanjing, 210009, Jiangsu, China.
Cui WangInstitute of Nephrology, Zhongda Hospital, Southeast University School of Medicine, 87 Ding Jia Qiao Road, Nanjing, 210009, Jiangsu, China.
Tao-Tao TangInstitute of Nephrology, Zhongda Hospital, Southeast University School of Medicine, 87 Ding Jia Qiao Road, Nanjing, 210009, Jiangsu, China.
Li-Ting WangInstitute of Nephrology, Zhongda Hospital, Southeast University School of Medicine, 87 Ding Jia Qiao Road, Nanjing, 210009, Jiangsu, China.
Kai-Yun SongInstitute of Nephrology, Zhongda Hospital, Southeast University School of Medicine, 87 Ding Jia Qiao Road, Nanjing, 210009, Jiangsu, China.
Ri-Ning TangInstitute of Nephrology, Zhongda Hospital, Southeast University School of Medicine, 87 Ding Jia Qiao Road, Nanjing, 210009, Jiangsu, China.
Hong LiuInstitute of Nephrology, Zhongda Hospital, Southeast University School of Medicine, 87 Ding Jia Qiao Road, Nanjing, 210009, Jiangsu, China.
Bi-Cheng LiuInstitute of Nephrology, Zhongda Hospital, Southeast University School of Medicine, 87 Ding Jia Qiao Road, Nanjing, 210009, Jiangsu, China.
Lin-Li LvInstitute of Nephrology, Zhongda Hospital, Southeast University School of Medicine, 87 Ding Jia Qiao Road, Nanjing, 210009, Jiangsu, China. lvlinli@seu.edu.cn.
Zhongda Hospital Southeast University · CN

Funding

International Cooperation and Exchange Programme 81720108007National Key R&D Program of China 2018YFC1314000National Natural Science Foundation of China 31671194National Natural Science Foundation of China 81970616National Natural Science Foundation of China 8203000544young medicine talents grant of jiangsu province QNRC2016818
6 · The paper itself

Abstract

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

methodsFourteen 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.

resultsThe 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.

conclusionsUrinary 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.

Indexed as

Chemokine CCL21Diabetes Mellitus, Type 2Diabetic NephropathiesExtracellular VesiclesAnimalsAquaporin 2BiomarkersHumansRatsRNA, MessengerAquaporin 2BiomarkersCCL21 protein, humanChemokine CCL21RNA, MessengerBiomarkerCCL21Diabetic nephropathyExosomesExtracellular vesiclesUrine

Identifiers

PMID34404433
PMCPMC8371892
OpenAlexW3196186912

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.