Evidence mapPaperPMID 36012674Full record

ArticleInternational journal of molecular sciences2022

The Histone Demethylase Inhibitor GSK-J4 Is a Therapeutic Target for the Kidney Fibrosis of Diabetic Kidney Disease via DKK1 Modulation.

Peir-Haur Hung, Yung-Chien Hsu, Tsung-Hsien Chen, Cheng Ho, Chun-Liang Lin

Open access · goldAbstract read
In one paragraph

Article in International journal of molecular sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
1.6field-weighted citation impact, top 16% 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

20 citing papers in PubMed, 23 citations in OpenAlex.

  1. [Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2026
    Article
  2. Post‑translational modifications in diabetic kidney disease (Review).International journal of molecular medicine · 2026
    Review
  3. Article
  4. Review
  5. Review
  6. Article
  7. Review
  8. Article
  9. Article
  10. Review
  11. Advances in the Epigenetic Mechanisms of Diabetic Nephropathy Pathogenesis.Diabetes, metabolic syndrome and obesity : targets and therapy · 2025
    Review
  12. Article
  13. Epigenetics-targeted drugs: current paradigms and future challenges.Signal transduction and targeted therapy · 2024
    Review
  14. Review
  15. Advances in the Pathogenesis of Diabetic Kidney Disease.International journal of molecular sciences · 2024
    Article
  16. Review
  17. Review
  18. Epigenetic modification in diabetic kidney disease.Frontiers in endocrinology · 2023
    Review
  19. Fibrosis-the tale of H3K27 histone methyltransferases and demethylases.Frontiers in cell and developmental biology · 2023
    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

5 authors at 3 institutions in 1 country.

Peir-Haur HungDepartment of Internal Medicine, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi 600566, Taiwan.ORCID 0000-0002-5963-6981
Yung-Chien HsuDepartment of Nephrology, Chang Gung Memorial Hospital, Chiayi 613016, Taiwan.
Tsung-Hsien ChenDepartment of Internal Medicine, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi 600566, Taiwan.ORCID 0000-0002-1542-1495
Cheng HoDivision of Endocrinology and Metabolism, Chang Gung Memorial Hospital, Chiayi 613016, Taiwan.
Chun-Liang LinDepartment of Nephrology, Chang Gung Memorial Hospital, Chiayi 613016, Taiwan.ORCID 0000-0002-5710-8405
Chiayi Chang Gung Memorial Hospital · TWChia-Yi Christian Hospital · TWChang Gung University · TW

Funding

Chang Gung Memorial Hospital at Chiayi, Taiwan CMRPG6K0231-3
6 · The paper itself

Abstract

Diabetic kidney disease (DKD) can cause inflammation and fibrosis, in addition to being the main complication of diabetes. Among many factors, epigenetic alterations in aberrant histone modifications play a key role in causing DKD. In this study, the mechanism of GSK-J4, a histone demethylase KDM6A inhibitor, was evaluated in streptozotocin-induced diabetic mice. It was confirmed that GSK-J4, via dickkopf-1 (DKK1) modulation, could significantly reduce proteinuria and glomerulosclerosis in diabetic mice. The mRNA accumulation levels of DKK1, TGF-β1, fibronectin, and collagen IV were significantly elevated in diabetic mice. In contrast, the mRNA accumulations of those genes were significantly reduced in diabetic mice treated with GSK-J4 compared to those in diabetic mice, relatively speaking. The protein accumulation levels of fibronectin and collagen IV were significantly elevated in diabetic mice. Furthermore, GSK-J4 attenuated the high glucose-induced expression of profibrotic factors in mesangial cells via DKK1. In conclusion, our study provides a novel strategy to eliminate fibrosis in the kidneys of DKD mice. Using GSK-J4 reduces DKK1 expression, thereby ameliorating renal insufficiency, glomerulosclerosis morphological abnormalities, inflammation, and fibrosis in diabetic mice.

Indexed as

BenzazepinesDiabetes Mellitus, ExperimentalDiabetic NephropathiesHistone DemethylasesIntercellular Signaling Peptides and ProteinsPyrimidinesAnimalsCollagenFibronectinsFibrosisInflammationKidneyMiceRNA, MessengerBenzazepinesCollagenDkk1 protein, mouseFibronectinsGSK-J4Histone DemethylasesIntercellular Signaling Peptides and ProteinsPyrimidinesRNA, Messengerdiabetic kidney diseaseDKK1fibrosishistone demethylaseinflammationstreptozotocin-induced diabetic mice

Identifiers

PMID36012674
PMCPMC9409090
OpenAlexW4292962592

What Socratic holds

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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.