Evidence map›Paper›PMID 22260450›Full record

ArticleAging cell2012

Klotho gene delivery suppresses Nox2 expression and attenuates oxidative stress in rat aortic smooth muscle cells via the cAMP-PKA pathway.

Yuhong Wang, Makoto Kuro-o, Zhongjie Sun

Open access · bronzeAbstract read
In one paragraph

Article in Aging cell, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.

0numbers the graph read from it
0cells of the map it votes in
75citing papers in PubMed
5.0field-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

75 citing papers in PubMed, 124 citations in OpenAlex.

  1. Effects of resveratrol supplementation on cardiac remodeling in hypertensive patients: a randomized controlled clinical trial.Hypertension research : official journal of the Japanese Society of Hypertension · 2023
    Trial
  2. Increased ATCell death & disease · 2020
    Trial
  3. Article
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  6. Frontiers in pharmacology · 2025
    Article
  7. Oxidative Stress in Kidney Injury and Hypertension.Antioxidants (Basel, Switzerland) · 2024
    Review
  8. Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article

15 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

3 authors at 2 institutions in 1 country.

Yuhong WangDepartment of Physiology, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
Makoto Kuro-o
Zhongjie Sun
University of Oklahoma Health Sciences Center · USThe University of Texas Southwestern Medical Center · US

Funding

Regulation of Blood Pressure by KlothoR01HL102074 · NHLBI · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI SUN, ZHONGJIE · 2011 to 2014
$2.1M
Molecular Mechanism of Arterial StiffeningR01HL105302 · NHLBI · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI SUN, ZHONGJIE · 2010 to 2014
$1.4M
NHLBI NIH HHS HL102074NHLBI NIH HHS HL105302NHLBI NIH HHS R01 HL102074NHLBI NIH HHS R01 HL105302
6 · The paper itself

Abstract

Klotho is a recently discovered anti-aging gene. The purpose of this study was to investigate whether klotho gene transfer attenuates superoxide production and oxidative stress in rat aorta smooth muscle (RASM) cells. RASM cells were transfected with AAV plasmids carrying mouse klotho full-length cDNA (mKL) or LacZ as a control. Klotho gene transfer increased klotho expression in RASM cells. Notably, klotho gene expression decreased Nox2 NADPH oxidase protein expression but did not affect Nox2 mRNA expression, suggesting that the inhibition may occur at the posttranscriptional level. Klotho gene transfer decreased intracellular superoxide production and oxidative stress in RASM cells. Klotho gene expression also significantly attenuated the angiotensin II (AngII)-induced superoxide production, oxidative damage, and apoptosis. Interestingly, klotho gene delivery dose dependently increased the intracellular cAMP level and PKA activity in RASM cells. Rp-cAMP, a competitive inhibitor of cAMP, abolished the klotho-induced increase in PKA activity, indicating that klotho activated PKA via cAMP. Notably, inhibition of cAMP-dependent PKA activity by RP-cAMP abolished klotho-induced inhibition of Nox2 protein expression, suggesting an important role of cAMP-dependent PKA in this process. This finding revealed a previously unidentified role of klotho in regulating Nox2 protein expression in RASM cells. Klotho not only downregulated Nox2 protein expression and intracellular superoxide production but also attenuated AngII-induced superoxide production, oxidative damage, and apoptosis. The klotho-induced suppression of Nox2 protein expression may be mediated by the cAMP-PKA pathway.

Indexed as

AnimalsAortaCyclic AMPCyclic AMP-Dependent Protein KinasesGene ExpressionGene Transfer TechniquesGlucuronidaseHumansKlotho ProteinsMiceMuscle, Smooth, VascularMyocytes, Smooth MuscleNADPH OxidasesOxidative StressRatsReactive Oxygen SpeciesCyclic AMPCyclic AMP-Dependent Protein KinasesGlucuronidaseKlotho ProteinsNADPH OxidasesReactive Oxygen Species

Identifiers

PMID22260450
PMCPMC3342395
OpenAlexW1500361177

What OpenQuestion holds

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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.