Evidence map›Paper›PMID 29491489›Full record

ArticleScientific reports2018

Genome-wide analysis revealed that DZNep reduces tubulointerstitial fibrosis via down-regulation of pro-fibrotic genes.

Imari Mimura, Yosuke Hirakawa, Yasuharu Kanki, Ryo Nakaki, Yutaka Suzuki, Tetsuhiro Tanaka, Hiroyuki Aburatani, Masaomi Nangaku

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.7field-weighted citation impact, top 18% 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

16 citing papers in PubMed, 24 citations in OpenAlex.

  1. Epigenetic memories induced by hypoxia in AKI-to-CKD transition.Clinical and experimental nephrology · 2025
    Review
  2. Article
  3. Review
  4. Article
  5. [Role of Histone Modifications in Acute Kidney Injury Progressing to Chronic Kidney Disease].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2023
    Article
  6. Sex-specific epigenetic programming in renal fibrosis and inflammation.American journal of physiology. Renal physiology · 2023
    Review
  7. Article
  8. Review
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  10. Review
  11. Article
  12. Review
  13. Article
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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

8 authors at 2 institutions in 1 country.

Imari MimuraDivision of Nephrology and Endocrinology, The University of Tokyo Graduate School of Medicine, Bunkyō, Japan.
Yosuke HirakawaDivision of Nephrology and Endocrinology, The University of Tokyo Graduate School of Medicine, Bunkyō, Japan.
Yasuharu KankiIsotope Science Center, The University of Tokyo, Bunkyō, Japan.
Ryo NakakiDivision of Genome Science, Research Center for Advanced Science and Technology, The University of Tokyo, Bunkyō, Japan.
Yutaka SuzukiGraduate School of Frontier Sciences, The University of Tokyo, Bunkyō, Japan.
Tetsuhiro TanakaDivision of Nephrology and Endocrinology, The University of Tokyo Graduate School of Medicine, Bunkyō, Japan.
Hiroyuki AburataniDivision of Genome Science, Research Center for Advanced Science and Technology, The University of Tokyo, Bunkyō, Japan.ORCID 0000-0003-0438-1544
Masaomi NangakuDivision of Nephrology and Endocrinology, The University of Tokyo Graduate School of Medicine, Bunkyō, Japan. mnangaku-tky@umin.ac.jp.
The University of Tokyo · JPBunkyo University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Tubulointerstitial fibrosis has been recently reported to be caused by the collapse of the epigenetic regulation of kidney diseases. We examined whether pharmacological inhibition of histone modification is effective against renal fibrosis. DZNep (3-deazaneplanocin A) was originally developed as an anti-cancer drug to inhibit the repressive histone mark, H3K27me3. We used a model of chronic tubulointerstitial fibrosis induced by unilateral ischaemia/reperfusion and administered DZNep intravenously to the mice for 8 weeks. We found DZNep contributes to the reduction of tubulointerstitial fibrosis. We selected only tubular cells from in vivo samples using laser-capture microdissection because epigenetic regulation is specific to the cell types, and we focused on the changes in the tubular cells. We performed a genome-wide analysis of tubular cells using high-throughput sequencing (RNA-seq) to identify novel epigenetic factors associated with renal fibrosis. We found that pro-fibrotic genes such as COL3A1 (collagen type 3a1) and TIMP2 (tissue inhibitor of metalloproteinase 2) were suppressed by DZNep in vivo. In addition, pro-fibrotic genes such as COL4A1 (collagen type 4a1), TIMP2 and MMP14 were down-regulated by DZNep in vitro. In conclusion, we found that pharmacological epigenetic modification by DZNep decreased the expression levels of fibrogenic genes in tubular cells and inhibited tubulointerstitial fibrosis.

Indexed as

GenomeAdenosineAnimalsBiomarkersCells, CulturedFibrosisGene Expression ProfilingGene Expression RegulationHumansKidney DiseasesMaleMiceMice, Inbred C57BLReperfusion Injury3-deazaneplanocinAdenosineBiomarkers

Identifiers

PMID29491489
PMCPMC5830881
OpenAlexW2794833446

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.