Evidence map›Paper›PMID 37016580›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2023

Epsin1-mediated exosomal sorting of Dll4 modulates the tubular-macrophage crosstalk in diabetic nephropathy.

Jia-Lu Liu, Lei Zhang, Ying Huang, Xiao-Hui Li, Yi-Fei Liu, Shu-Min Zhang, Yue-E Zhao, Xiao-Jun Chen, Yu Liu, Li-Yu He and 4 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed, 1 pooled it
6.0field-weighted citation impact, top 3% 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

32 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 citations in OpenAlex.

  1. Pooled it
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  5. Review
  6. Article
  7. Review
  8. Review
  9. Article
  10. Article
  11. Review
  12. Article
  13. Exosomes applications in kidney diseases.Molecular biology reports · 2025
    Review
  14. Review
  15. m6A demethylase Fto inhibited macrophage activation and glycolysis in diabetic nephropathy via m6A/Npas2/Hif-1α axis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025
    Article
  16. Article
  17. Review
  18. Research progress on small extracellular vesicles in diabetic nephropathy.Frontiers in cell and developmental biology · 2025
    Review
  19. Urinary exosomes as promising biomarkers for early kidney disease detection.American journal of clinical and experimental urology · 2025
    Review
  20. Review
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

14 authors at 1 institution in 2 countries.

Jia-Lu LiuDepartment of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
Lei ZhangDepartment of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
Ying HuangDepartment of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
Xiao-Hui LiDepartment of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
Yi-Fei LiuDepartment of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
Shu-Min ZhangDepartment of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
Yue-E ZhaoDepartment of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
Xiao-Jun ChenDepartment of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
Yu LiuDepartment of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
Li-Yu HeDepartment of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
Zheng DongDepartment of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China; Department of Cellular Biology and Anatomy, Medical College of Georgia at Augusta University, Augusta, GA, USA; Charlie Norwood VA Medical Center, Augusta, GA, USA.
Fu-You LiuDepartment of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
Lin SunDepartment of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
Li XiaoDepartment of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China. Electronic address: xiaolizndx@csu.edu.cn.
Central South University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Tubular epithelial cells (TECs) play critical roles in the development of diabetic nephropathy (DN), and can activate macrophages through the secretion of exosomes. However, the mechanism(s) of TEC-exosomes in macrophage activation under DN remains unknown. By mass spectrometry, 1,644 differentially expressed proteins, especially Dll4, were detected in the urine exosomes of DN patients compared with controls, which was confirmed by western blot assay. Elevated Epsin1 and Dll4/N1ICD expression was observed in kidney tissues in both DN patients and db/db mice and was positively associated with tubulointerstitial damage. Exosomes from high glucose (HG)-treated tubular cells (HK-2) with Epsin1 knockdown (KD) ameliorated macrophage activation, TNF-α, and IL-6 expression, and tubulointerstitial damage in C57BL/6 mice in vivo. In an in vitro study, enriched Dll4 was confirmed in HK-2 cells stimulated with HG, which was captured by THP-1 cells and promoted M1 macrophage activation. In addition, Epsin1 modulated the content of Dll4 in TEC-exosomes stimulated with HG. TEC-exosomes with Epsin1-KD significantly inhibited N1ICD activation and iNOS expression in THP-1 cells compared with incubation with HG alone. These findings suggested that Epsin1 could modulate tubular-macrophage crosstalk in DN by mediating exosomal sorting of Dll4 and Notch1 activation.

Indexed as

Diabetes MellitusDiabetic NephropathiesAdaptor Proteins, Signal TransducingAdaptor Proteins, Vesicular TransportAnimalsCalcium-Binding ProteinsCell MovementEpithelial CellsGlucoseMacrophagesMiceMice, Inbred C57BLAdaptor Proteins, Signal TransducingAdaptor Proteins, Vesicular TransportCalcium-Binding ProteinsDLL4 protein, mouseepsinGlucosediabetic nephropathyDll4Epsin1exosomeinflammation

Identifiers

PMID37016580
PMCPMC10188907
OpenAlexW4362575860

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.