Evidence map›Paper›PMID 25892014›Full record

ArticleInternational journal of molecular medicine2015

Epigenetic repression of Krüppel-like factor 4 through Dnmt1 contributes to EMT in renal fibrosis.

Xiangcheng Xiao, Wenbin Tang, Qiongjing Yuan, Ling Peng, Pingping Yu

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PubMed Full text at PMC Publisher
In one paragraph

Article in International journal of molecular medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed, 1 pooled it
2.9field-weighted citation impact, top 9% 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

36 citing papers in PubMed, 1 synthesis or guideline pooled it, 58 citations in OpenAlex.

  1. Pooled it
  2. Review
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  7. Review
  8. Kidney fibrosis: from mechanisms to therapeutic medicines.Signal transduction and targeted therapy · 2023
    Review
  9. Epigenetics as a versatile regulator of fibrosis.Journal of translational medicine · 2023
    Review
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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

5 authors at 1 institution in 1 country.

Xiangcheng XiaoDepartment of Nephrology, Xiangya Hospital, Central South University, Changsha, Hunan 410000, P.R. China.
Wenbin TangDepartment of Nephrology, Xiangya Hospital, Central South University, Changsha, Hunan 410000, P.R. China.
Qiongjing YuanDepartment of Nephrology, Xiangya Hospital, Central South University, Changsha, Hunan 410000, P.R. China.
Ling PengThe Nephrotic Laboratory of Xiangya Hospital, Central South University, Changsha, Hunan 410000, P.R. China.
Pingping YuDepartment of Geriatrics, Xiangya Hospital, Central South University, Changsha, Hunan 410000, P.R. China.
Central South University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Krüppel-like factor 4 (KLF4) is a transcription factor which plays divergent roles in a number of physiological or pathological process. However, the expression and role of KLF4 in renal fibrosis remain undetermined. The aim of the present study was to determine the epigenetic alterations of KLF4 and its potential role and mechanisms of action in epithelial-to-mesenchymal transition (EMT) in renal fibrosis. The hypermethylation of the KLF4 promoter accompanied by a decrease in KLF4 expression were observed in mice subjected to unilateral ureteral obstruction (UUO) and in HK-2 cells stimulated with transforming growth factor (TGF)-β1. However, treatment with 5-aza-2'-deoxycytidine attenuated the TGF-β1-induced downregulation of KLF4 and E-cadherin and the upregulation of α-smooth muscle actin (α-SMA) in the HK-2 cells. DNA methyltransferase 1 (Dnmt1) participated in the TGF-β1-mediated hypermethylation of the KLF4 promoter in the HK-2 cells. In addition, functional analysis demonstrated that the overexpression of KLF4 led to an increase in the expression of E-cadherin and zonula occludens-l (ZO-1), and a decrease in the expression of α-SMA and fibroblast-specific protein 1 (FSP-1), thus reversing the effects of the suppression of KLF4. These data suggest that KLF4 inhibits the progression of EMT in renal epithelial cells. In conclusion, our findings demonstrate that KLF4 is downregulated during EMT in renal fibrosis in vivo and in vitro; thus, KLF4 functions as a suppressor of renal fibrogenesis. The hypermethylation of KLF4 directly mediated by Dnmt1 contributes to the progression of EMT in renal epithelial cells. KLF4 promoter methylation may thus be a promising diagnostic marker or therapeutic target in renal fibrosis.

Indexed as

Down-RegulationEpithelial-Mesenchymal TransitionAnimalsDNA (Cytosine-5-)-Methyltransferase 1DNA (Cytosine-5-)-MethyltransferasesDNA MethylationFibrosisHumansKidney DiseasesKruppel-Like Factor 4Kruppel-Like Transcription FactorsMaleMicePromoter Regions, GeneticTransforming Growth Factor beta1Ureteral ObstructionDNA (Cytosine-5-)-Methyltransferase 1DNA (Cytosine-5-)-MethyltransferasesDNMT1 protein, humanDnmt1 protein, mouseKLF4 protein, humanKlf4 protein, mouseKruppel-Like Factor 4Kruppel-Like Transcription FactorsTGFB1 protein, humanTgfb1 protein, mouseTransforming Growth Factor beta1

Identifiers

PMID25892014
PMCPMC4432929
OpenAlexW2137622675

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.