Evidence map›Paper›PMID 27448998›Full record

ArticlePflugers Archiv : European journal of physiology2016

Klotho modulates FGF23-mediated NO synthesis and oxidative stress in human coronary artery endothelial cells.

Beatrice Richter, Jacqueline Haller, Dieter Haffner, Maren Leifheit-Nestler

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Article in Pflugers Archiv : European journal of physiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
65citing papers in PubMed, 1 pooled it
8.2field-weighted citation impact, top 2% 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

65 citing papers in PubMed, 1 synthesis or guideline pooled it, 109 citations in OpenAlex.

  1. Pooled it
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  12. Emerging concepts on the FGF23 regulation and activity.Molecular and cellular biochemistry · 2025
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5 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

4 authors at 1 institution in 1 country.

Beatrice RichterDepartment of Pediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
Jacqueline HallerDepartment of Pediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
Dieter HaffnerDepartment of Pediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
Maren Leifheit-NestlerDepartment of Pediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany. leifheit-nestler.maren@mh-hannover.de.
Medizinische Hochschule Hannover · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Chronic kidney disease (CKD) is a state of Klotho deficiency and excess of the phosphaturic hormone fibroblast growth factor 23 (FGF23). Both dysregulations were shown to be associated with endothelial dysfunction in humans, but direct vascular effects of FGF23 remain largely elusive. In vitro experiments were performed to assess the effects of FGF23 (10 ng/mL) in relation to its co-receptor Klotho on nitric oxide (NO) synthesis and reactive oxygen species (ROS) formation and detoxification in human coronary artery endothelial cells (HCAEC). Membrane-bound Klotho is expressed in HCAEC, and FGF23 increases the expression of the Klotho shedding protease ADAM17, and consequently the secretion of soluble Klotho. FGF23 activates FGF receptor 1 and stimulates NO release via Akt-dependent activation of endothelial NO synthase (eNOS). Both FGF receptor (FGFR)-dependent ROS formation via activation of NADPH oxidase 2 (Nox2) as well as ROS degradation via superoxide dismutase 2 (SOD2) and catalase (CAT) is stimulated by FGF23. Pre-incubation with a Klotho inhibitor blunts the FGF23-stimulated Akt-eNOS activation and NO synthesis, and decreases ROS degradation by blocking SOD2 and CAT enzymes, whereas FGF23-stimulated ROS synthesis via Nox2 is unaffected, resulting in low NO bioavailability and increased oxidative stress. Our data indicate that in the presence of Klotho, FGF23 induces NO release in HCAEC and its stimulating effects on ROS production are counterbalanced by increased ROS degradation. In states of Klotho deficiency, e.g., CKD, FGF23-mediated NO synthesis is blunted and ROS formation overrules ROS degradation. Thus, FGF23 excess may primarily promote oxidative stress and thus endothelial dysfunction.

Indexed as

Oxidative StressADAM17 ProteinCatalaseCells, CulturedCoronary VesselsEndothelial CellsEndothelium, VascularFibroblast Growth Factor-23Fibroblast Growth FactorsGlucuronidaseHEK293 CellsHumansKlotho ProteinsMembrane GlycoproteinsNADPH Oxidase 2NADPH OxidasesADAM17 ProteinADAM17 protein, humanCatalaseCYBB protein, humanFGF23 protein, humanFibroblast Growth Factor-23Fibroblast Growth FactorsGlucuronidaseKlotho ProteinsMembrane GlycoproteinsNADPH Oxidase 2NADPH OxidasesNitric OxideNitric Oxide Synthase Type IIIProto-Oncogene Proteins c-aktSuperoxide DismutaseSuperoxide Dismutase 2Fibroblast growth factor 23KlothoNitric oxide synthesisOxidative stressReactive oxygen species formation

Identifiers

PMID27448998
OpenAlexW2502308186

What OpenQuestion holds

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Read underepoch 390

Registered trials

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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.