Evidence mapPaperPMID 20019166Full record

ArticleJournal of the American Society of Nephrology : JASN2010

Dickkopf-1 promotes hyperglycemia-induced accumulation of mesangial matrix and renal dysfunction.

Chun-Liang Lin, Jeng-Yi Wang, Jih-Yang Ko, Yu-Ting Huang, Yu-Hsia Kuo, Feng-Sheng Wang

Open access · bronzeAbstract read
In one paragraph

Article in Journal of the American Society of Nephrology : JASN, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.

0numbers the graph read from it
0cells of the map it votes in
62citing papers in PubMed
2.0field-weighted citation impact, top 13% 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

62 citing papers in PubMed, 96 citations in OpenAlex.

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  14. Pathomechanisms of Diabetic Kidney Disease.Journal of clinical medicine · 2023
    Review
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2 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

6 authors at 5 institutions in 2 countries.

Chun-Liang LinDepartment of Nephrology, Chang Gung Memorial Hospital, Chiayi,Taiwan.
Jeng-Yi Wang
Jih-Yang Ko
Yu-Ting Huang
Yu-Hsia Kuo
Feng-Sheng Wang
Kaohsiung Chang Gung Memorial Hospital · TWChang Gung Memorial Hospital · TWChiayi Chang Gung Memorial Hospital · TWGTx (United States) · USOrthopedic One · US

Funding

Howard Hughes Medical Institute
6 · The paper itself

Abstract

Wnt/beta-catenin signaling mediates renal fibrosis in several model systems including diabetic nephropathy. Dickkopf-1 (DKK-1) is an endogenous inhibitor of Wnt/beta-catenin signaling, but whether DKK-1 modulates diabetic nephropathy is unknown. Here, we studied whether DKK-1 participates in high glucose (HG)-induced expression of profibrotic factors and renal damage. In vitro, HG increased expression of DKK1, receptor Kremen-2, TGF-beta1, and fibronectin in mesangial cells. Loss and gain of DKK1 function modulated HG-mediated c-Jun, TGF-beta1, and fibronectin expression. DKK1 mediated HG-induced phosphorylation of Ser45-beta-catenin and reduction of nuclear beta-catenin levels, but not phosphorylation of ERK kinase. Wnt3a protein and the beta-catenin (Delta45) mutation increased nuclear beta-catenin but abrogated HG-induced DKK1 and fibronectin expression. Exogenous DKK1 antisense oligonucleotide attenuated the increase in both serum DKK1 and urinary protein excretion in streptozotocin-induced diabetic rats. Knocking down DKK1 inhibited mesangial expression of TGF-beta1 and fibronectin and reduced both the glomerular volume and deposition of mesangial matrix in diabetic kidneys. Taken together, DKK1 mediates HG-induced destabilization of beta-catenin and matrix accumulation in mesangial cells. Knocking down DKK1 prevents diabetes-induced renal dysfunction and microstructure deterioration, suggesting that inhibition of DKK1offers therapeutic potential for diabetic nephropathy.

Indexed as

Animalsbeta CateninCells, CulturedDiabetes Mellitus, ExperimentalDiabetic NephropathiesDisease Models, AnimalExtracellular MatrixExtracellular Signal-Regulated MAP KinasesFibronectinsFibrosisGlomerular MesangiumHyperglycemiaIntercellular Signaling Peptides and ProteinsKidneyMaleRatsbeta CateninDkk1 protein, ratExtracellular Signal-Regulated MAP KinasesFibronectinsIntercellular Signaling Peptides and ProteinsKremen2 protein, ratReceptors, Cell SurfaceStreptozocinTransforming Growth Factor beta1

Identifiers

PMID20019166
PMCPMC2799277
OpenAlexW2146314322

What Socratic holds

Textmetadata
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 Socratic graph.