Evidence map›Paper›PMID 23928372›Full record

ArticleEndocrinology2013

Genetic deficiency of anti-aging gene klotho exacerbates early nephropathy in STZ-induced diabetes in male mice.

Yi Lin, Makoto Kuro-o, Zhongjie Sun

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Endocrinology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed, 1 pooled it
2.6field-weighted citation impact, top 11% 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

42 citing papers in PubMed, 1 synthesis or guideline pooled it, 85 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Integrative Approaches to Treating Cellular Senescence in Kidney Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Review
  4. Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. Review
  10. [Research Progress in Stress-Induced Senescence of Renal Tubular Cells in Diabetic Nephropathy].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2023
    Article
  11. Review
  12. Article
  13. Article
  14. Review
  15. Article
  16. Review
  17. Article
  18. Article
  19. Review
  20. 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

3 authors at 2 institutions in 1 country.

Yi LinMD, PhD, FAHA, Professor of Physiology, Director, The Robert and Mary Cade Laboratory, BMSB 662A, Box 26901, Department of Physiology, College of Medicine, University of Oklahoma Health Sciences Center, 940 S. L. Young Boulevard, Oklahoma City, OK 73126-0901. Zhongjie-sun@ouhsc.edu.
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 Kidney AgingR01DK093403 · NIDDK · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI SUN, ZHONGJIE · 2012 to 2016
$1.6M
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 HL105302NIDDK NIH HHS DK 093403NIDDK NIH HHS R01 DK093403
6 · The paper itself

Abstract

Klotho is a recently discovered anti-aging gene and is primarily expressed in kidneys. In humans, the klotho level decreases with age whereas the prevalence of chronic kidney disease (CKD) increases with age. Diabetic nephropathy is the most common form of CKD, which leads to end-stage renal disease. A decrease in klotho has been found in kidneys of patients with diabetic nephropathy. The purpose of this study is to assess whether klotho gene deficiency affects early diabetic nephropathy in a mouse of model of type 1 diabetes induced by streptozotocin (STZ). Male KL(+/-) mutant and wild-type mice (6-8 weeks) were injected with multiple low doses of STZ. Renal functions and renal blood flow were assessed. Kidneys were collected for histological examination and molecular assays of TGFβ1 and mammalian targets of rapamycin (mTOR) signaling. Klotho deficiency in KL(+/-) mutant mice exacerbated STZ-induced increases in urine albumin, blood urea nitrogen, expansion of mesangial matrix in renal glomeruli, and kidney hypertrophy, suggesting a protective role of klotho in kidney function and structure. Klotho deficiency did not affect renal blood flow. Notably, klotho deficiency significantly increased phosphorylation of Smad2, indicating enhanced TGFβ1 signaling in kidneys. Klotho deficiency also increased phosphorylation of mTOR and S6 (a downstream effector of mTOR), indicating enhanced mTOR signaling in kidneys of early diabetic mice. Thus, klotho gene deficiency may make kidneys more susceptible to diabetic injury. Klotho gene deficiency exacerbated early diabetic nephropathy via enhancing both TGFβ1 and mTOR signaling in kidneys.

Indexed as

AnimalsDiabetes Mellitus, Type 1Diabetic NephropathiesDisease SusceptibilityGlucuronidaseHeterozygoteHypertrophyKidneyKlotho ProteinsMaleMiceMice, 129 StrainMice, Mutant StrainsPhosphorylationProtein Processing, Post-TranslationalRenal InsufficiencyGlucuronidaseKlotho ProteinsmTOR protein, mouseRibosomal Protein S6ribosomal protein S6, mouseSmad2 ProteinSmad2 protein, mouseTgfb1 protein, mouseTOR Serine-Threonine KinasesTransforming Growth Factor beta1

Identifiers

PMID23928372
PMCPMC3776873
OpenAlexW2008545825

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.