Evidence map›Paper›PMID 26224753›Full record

ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2015

DNA hypermethylation in hyperhomocysteinemia contributes to abnormal extracellular matrix metabolism in the kidney.

Sathnur Pushpakumar, Sourav Kundu, Nithya Narayanan, Utpal Sen

Abstract read
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In one paragraph

Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
5.4field-weighted citation impact, top 4% 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

29 citing papers in PubMed, 40 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Epigenetics in kidney diseases.Advances in clinical chemistry · 2021
    Review
  11. Article
  12. Review
  13. Article
  14. Faulty homocysteine recycling in diabetic retinopathy.Eye and vision (London, England) · 2020
    Article
  15. Article
  16. Epigenetic Mechanisms and Hypertension.Hypertension (Dallas, Tex. : 1979) · 2018
    Review
  17. Review
  18. Review
  19. Article
  20. Ten-eleven translocation 2 demethylates theThe Journal of biological chemistry · 2018
    Article
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

4 authors at 1 institution in 1 country.

Sathnur PushpakumarDepartment of Physiology and Biophysics, University of Louisville School of Medicine, Louisville, Kentucky, USA sbpush01@louisville.edu u0sen001@louisville.edu.
Sourav KunduDepartment of Physiology and Biophysics, University of Louisville School of Medicine, Louisville, Kentucky, USA.
Nithya NarayananDepartment of Physiology and Biophysics, University of Louisville School of Medicine, Louisville, Kentucky, USA.
Utpal SenDepartment of Physiology and Biophysics, University of Louisville School of Medicine, Louisville, Kentucky, USA sbpush01@louisville.edu u0sen001@louisville.edu.
University of Louisville · US

Funding

Homocysteine & Angiotensin II in Renovascular RemodelingR01HL104103 · NHLBI · UNIVERSITY OF LOUISVILLE · PI SEN, UTPAL · 2011 to 2015
$1.8M
NHLBI NIH HHS HL-104103NHLBI NIH HHS R01 HL104103
6 · The paper itself

Abstract

Hyperhomocysteinemia (HHcy) is prevalent in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD). Emerging studies suggest that epigenetic mechanisms contribute to the development and progression of fibrosis in CKD. HHcy and its intermediates are known to alter the DNA methylation pattern, which is a critical regulator of epigenetic information. In this study, we hypothesized that HHcy causes renovascular remodeling by DNA hypermethylation, leading to glomerulosclerosis. We also evaluated whether the DNA methylation inhibitor, 5-aza-2'-deoxycytidine (5-Aza) could modulate extracellular matrix (ECM) metabolism and reduce renovascular fibrosis. C57BL/6J (wild-type) and cystathionine-β-synthase (CBS(+/-)) mice, treated without or with 5-Aza (0.5 mg/kg body weight, i.p.), were used. CBS(+/-) mice showed high plasma Hcy levels, hypertension, and significant glomerular and arteriolar injury. 5-Aza treatment normalized blood pressure and reversed renal injury. CBS(+/-) mice showed global hypermethylation and up-regulation of DNA methyltransferase-1 and -3a. Methylation-specific PCR showed an imbalance between matrix metalloproteinase (MMP)-9 and tissue inhibitor of metalloproteinase (TIMP)-1 and -2 and also increased collagen and galectin-3 expression. 5-Aza reduced abnormal DNA methylation and restored the MMP-9/TIMP-1, -2 balance. In conclusion, our data suggest that during HHcy, abnormal DNA methylation and an imbalance between MMP-9 and TIMP-1 and -2 lead to ECM remodeling and renal fibrosis.

Indexed as

DNA MethylationAcute Kidney InjuryAnimalsBlood PressureCollagenCystathionine beta-SynthaseCytidine MonophosphateDNA (Cytosine-5-)-MethyltransferasesDNA Methyltransferase 3AExtracellular MatrixFibrosisGalectin 3HyperhomocysteinemiaKidneyMatrix Metalloproteinase 9Mice5'-azacytidine 5'-monophosphateCollagenCystathionine beta-SynthaseCytidine MonophosphateDNA (Cytosine-5-)-MethyltransferasesDNA Methyltransferase 3AGalectin 3Lgals3 protein, mouseMatrix Metalloproteinase 9Mmp9 protein, mouseTimp1 protein, mouseTissue Inhibitor of Metalloproteinase-1Tissue Inhibitor of Metalloproteinase-25-aza-2′-deoxycytidineepigeneticsmatrix metalloproteinaserenal fibrosis

Identifiers

PMID26224753
PMCPMC4608914
OpenAlexW1925280967

What OpenQuestion 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 OpenQuestion graph.