Evidence map›Paper›PMID 30251773›Full record

ArticleActa physiologica (Oxford, England)2019

Klotho protein supplementation reduces blood pressure and renal hypertrophy in db/db mice, a model of type 2 diabetes.

Tsuneo Takenaka, Hiroyuki Kobori, Takashi Miyazaki, Hiromichi Suzuki, Akira Nishiyama, Naohito Ishii, Maho Yamashita, Matsuhiko Hayashi

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Acta physiologica (Oxford, England), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed, 2 pooled it
4.1field-weighted citation impact, top 5% 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

31 citing papers in PubMed, 2 syntheses or guidelines pooled it, 71 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Review
  4. Integrative Approaches to Treating Cellular Senescence in Kidney Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
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  14. TheIndian journal of clinical biochemistry : IJCB · 2023
    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 5 institutions in 1 country.

Tsuneo TakenakaInternational University of Health and Welfare, Minato, Japan.ORCID 0000-0002-3383-1340
Hiroyuki KoboriInternational University of Health and Welfare, Minato, Japan.
Takashi MiyazakiSaitama Medical University, Moroyama, Japan.
Hiromichi SuzukiSaitama Medical University, Moroyama, Japan.
Akira NishiyamaKagawa University, Takamatsu, Japan.
Naohito IshiiKitasato University, Sagamihara, Japan.
Maho YamashitaKeio University, Shinjuku, Japan.
Matsuhiko HayashiKeio University, Shinjuku, Japan.
International University of Health and Welfare · JPKeio University Hospital · JPSaitama Medical University · JPKagawa University · JPKitasato University · JP

Funding

Intrarenal Augmentation of Angiotensinogen by Ang IIR01DK072408 · NIDDK · TULANE UNIVERSITY OF LOUISIANA · PI NAVAR, LUIS GABRIEL · 2006 to 2010
$1.2M
Japan Society for the Promotion of Science 16K3457190NIDDK NIH HHS R01 DK072408
6 · The paper itself

Abstract

aimsKlotho interacts with various membrane proteins, such as receptors for transforming growth factor (TGF)-β and insulin-like growth factor (IGF), to alter their function. Renal expression of klotho is diminished in diabetes. The present study examined whether exogenous klotho protein supplementation ameliorates kidney injury and renin-angiotensin system (RAS) in db/db mice.

methodsWe investigated the effects of klotho supplementation on diabetic kidney injury and RAS. Recombinant human klotho protein (10 μg/kg/d) was administered to db/db mice daily.

resultsKlotho protein supplementation reduced kidney weight, systolic blood pressure (SBP), albuminuria, glomerular filtration rate, and 8-epi-prostaglandin F2α excretion without affecting body weight. Although klotho supplementation did not alter glycated albumin, it reduced renal angiotensin II levels associated with reduced renal expression of angiotensinogen. Klotho supplementation improved renal expression of superoxide dismutase (SOD), and endogenous renal expression of klotho. Klotho supplementation reduced the levels of hypoxia-inducible factor, phosphorylated Akt, and phosphorylated mTOR and decreased the renal expression of TGF-β, tumour necrosis factor (TNF), and fibronectin.

conclusionsThese data indicate that klotho supplementation reduces blood pressure and albuminuria along with ameliorating renal RAS activation in db/db mice. Furthermore, these results suggest that klotho inhibits IGF signalling, induces SOD expression to reduce oxidative stress, and suppresses Akt-mTOR signalling to inhibit abnormal kidney growth. Collectively, the results suggest that klotho inhibits TGF-β and TNF signalling, resulting in a decline in renal fibrosis.

Indexed as

AnimalsBlood PressureDiabetes Mellitus, Type 2Diabetic NephropathiesGlomerular Filtration RateGlucuronidaseHypertrophyKidneyKlotho ProteinsMaleMiceRenin-Angiotensin SystemSignal TransductionGlucuronidaseKlotho Proteinsepithelial-mesenchymal transitioninsulin-like growth factormTORsuperoxide dismutasetransforming growth factortumour necrosis factor

Identifiers

PMID30251773
PMCPMC6335176
OpenAlexW2892494579

What OpenQuestion holds

Textmetadata
LicenceTDM
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.