Evidence map›Paper›PMID 20682692›Full record

ArticleDiabetes2010

Blockade of endothelial-mesenchymal transition by a Smad3 inhibitor delays the early development of streptozotocin-induced diabetic nephropathy.

Jinhua Li, Xinli Qu, Jun Yao, Georgina Caruana, Sharon D Ricardo, Yasuhiko Yamamoto, Hiroshi Yamamoto, John F Bertram

Open access · bronzeAbstract read
In one paragraph

Article in Diabetes, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 159 papers.

0numbers the graph read from it
0cells of the map it votes in
159citing papers in PubMed
6.9field-weighted citation impact, top 2% 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

159 citing papers in PubMed, 250 citations in OpenAlex.

  1. Wound Healing and Angiogenic Profiling of Dermal Endothelial Cells Isolated From People With Type 2 Diabetes.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
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  7. Endothelial to mesenchymal transition: a central mechanism in diabetes-induced vascular pathology.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2025
    Review
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  9. Article
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  12. Adenosine ACells · 2025
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99 more citing papers are in PubMed but not listed here.

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

8 authors at 2 institutions in 2 countries.

Jinhua LiDepartment of Anatomy and Developmental Biology, Monash University, Victoria, Australia. jinhua.li@med.monash.edu.au
Xinli Qu
Jun Yao
Georgina Caruana
Sharon D Ricardo
Yasuhiko Yamamoto
Hiroshi Yamamoto
John F Bertram
Monash University · AUKanazawa University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveA multicenter, controlled trial showed that early blockade of the renin-angiotensin system in patients with type 1 diabetes and normoalbuminuria did not retard the progression of nephropathy, suggesting that other mechanism(s) are involved in the pathogenesis of early diabetic nephropathy (diabetic nephropathy). We have previously demonstrated that endothelial-mesenchymal-transition (EndoMT) contributes to the early development of renal interstitial fibrosis independently of microalbuminuria in mice with streptozotocin (STZ)-induced diabetes. In the present study, we hypothesized that blocking EndoMT reduces the early development of diabetic nephropathy. RESEARCH DESIGN AND

methodsEndoMT was induced in a mouse pancreatic microvascular endothelial cell line (MMEC) in the presence of advanced glycation end products (AGEs) and in the endothelial lineage-traceble mouse line Tie2-Cre;Loxp-EGFP by administration of AGEs, with nonglycated mouse albumin serving as a control. Phosphorylated Smad3 was detected by immunoprecipitation/Western blotting and confocal microscopy. Blocking studies using receptor for AGE siRNA and a specific inhibitor of Smad3 (SIS3) were performed in MMECs and in STZ-induced diabetic nephropathy in Tie2-Cre;Loxp-EGFP mice.

resultsConfocal microscopy and real-time PCR demonstrated that AGEs induced EndoMT in MMECs and in Tie2-Cre;Loxp-EGFP mice. Immunoprecipitation/Western blotting showed that Smad3 was activated by AGEs but was inhibited by SIS3 in MMECs and in STZ-induced diabetic nephropathy. Confocal microscopy and real-time PCR further demonstrated that SIS3 abrogated EndoMT, reduced renal fibrosis, and retarded progression of nephropathy.

conclusionsEndoMT is a novel pathway leading to early development of diabetic nephropathy. Blockade of EndoMT by SIS3 may provide a new strategy to retard the progression of diabetic nephropathy and other diabetes complications.

Indexed as

AnimalsDiabetes Mellitus, ExperimentalDiabetic NephropathiesEndothelium, VascularExtracellular Matrix ProteinsGene Knockdown TechniquesGreen Fluorescent ProteinsKidneyMaleMesodermMiceMicroscopy, ConfocalPancreasPolymerase Chain ReactionProtein-Lysine 6-OxidaseReceptor for Advanced Glycation End Productsenhanced green fluorescent proteinExtracellular Matrix ProteinsGreen Fluorescent ProteinsLox protein, mouseProtein-Lysine 6-OxidaseReceptor for Advanced Glycation End ProductsReceptors, ImmunologicReceptor, TIE-2RNARNA, Small InterferingSerum AlbuminSmad2 ProteinSmad2 protein, mouseSmad3 ProteinSmad3 protein, mouseStreptozocin

Identifiers

PMID20682692
PMCPMC3279546
OpenAlexW2138991213

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.