Evidence map›Paper›PMID 37681408›Full record

ArticleJCI insight2023

1,25-Dihydroxyvitamin D3 regulates furin-mediated FGF23 cleavage.

Han Xie, Isinsu Bastepe, Wen Zhou, Birol Ay, Zara Ceraj, Ignacio A Portales-Castillo, Eva S Liu, Sherri-Ann M Burnett-Bowie, Harald Jüppner, Eugene P Rhee and 2 more

Open access · goldAbstract read
In one paragraph

Article in JCI insight, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
2.8field-weighted citation impact, top 9% 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

6 citing papers in PubMed, 14 citations in OpenAlex.

  1. Article
  2. Review
  3. The vitamin DAmerican journal of physiology. Cell physiology · 2025
    Article
  4. Article
  5. Non-Classical Effects of FGF23: Molecular and Clinical Features.International journal of molecular sciences · 2024
    Review
  6. 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

12 authors at 3 institutions in 1 country.

Han XieNephrology Division and.
Isinsu BastepeNephrology Division and.
Wen ZhouNephrology Division and.
Birol AyEndocrine Division, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Zara CerajNephrology Division and.
Ignacio A Portales-CastilloNephrology Division and.
Eva S LiuEndocrine Division, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Sherri-Ann M Burnett-BowieEndocrine Division, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Harald JüppnerEndocrine Division, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Eugene P RheeNephrology Division and.
Murat BastepeEndocrine Division, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Petra SimicNephrology Division and.
Massachusetts General Hospital · USBrigham and Women's Hospital · USHarvard University · US

Funding

Translational Imaging and Phenotyping CoreP30AR075042 · NIAMS · MASSACHUSETTS GENERAL HOSPITAL · PI MARY L BOUXSEIN, PAOLA DIVIETI PAJEVIC · 2019 to 2026
$7.4M
PTH/PTHRP RECEPTOR DEFECTS IN PSEUDOHYPOPARATHYROIDISMR01DK046718 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI JUEPPNER, HARALD W. · 1993 to 2024
$6.0M
Development of enthesopathy in the mouse model of X-linked hypophosphatemia (XLH)R01AR076973 · NIAMS · BRIGHAM AND WOMEN'S HOSPITAL · PI Eva S. Liu · 2021 to 2026
$2.4M
Skeletal FGF23 production mediated by GPCR/Gq/PKC signalingR01DK121776 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI BASTEPE, MURAT · 2020 to 2024
$2.4M
Metabolomics of CKD and CKD ProgressionU01DK106981 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI RHEE, EUGENE P. · 2015 to 2019
$2.2M
Kidney Glycolysis as the Mammalian Phosphate SensorR01DK130291 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI RHEE, EUGENE P. · 2022 to 2025
$1.9M
Lysophosphatidic acid (LPA) is a novel FGF23 regulator in acute kidney injury.K08DK124568 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI SIMIC, PETRA · 2020 to 2024
$866k
NIAMS NIH HHS P30 AR075042NIAMS NIH HHS R01 AR076973NIDDK NIH HHS K08 DK124568NIDDK NIH HHS R01 DK046718NIDDK NIH HHS R01 DK121776NIDDK NIH HHS R01 DK130291NIDDK NIH HHS U01 DK106981
6 · The paper itself

Abstract

Intact fibroblast growth factor 23 (iFGF23) is a phosphaturic hormone that is cleaved by furin into N-terminal and C-terminal fragments. Several studies have implicated vitamin D in regulating furin in infections. Thus, we investigated the effect of 1,25-dihydroxyvitamin D3 [1,25(OH)2D] and the vitamin D receptor (VDR) on furin-mediated iFGF23 cleavage. Mice lacking VDR (Vdr-/-) had a 25-fold increase in iFGF23 cleavage, with increased furin levels and activity compared with wild-type (WT) littermates. Inhibition of furin activity blocked the increase in iFGF23 cleavage in Vdr-/- animals and in a Vdr-knockdown osteocyte OCY454 cell line. Chromatin immunoprecipitation revealed VDR binding to DNA upstream of the Furin gene, with more transcription in the absence of VDR. In WT mice, furin inhibition reduced iFGF23 cleavage, increased iFGF23, and reduced serum phosphate levels. Similarly, 1,25(OH)2D reduced furin activity, decreased iFGF23 cleavage, and increased total FGF23. In a post hoc analysis of a randomized clinical trial, we found that ergocalciferol treatment, which increased serum 1,25(OH)2D, significantly decreased serum furin activity and iFGF23 cleavage, compared with placebo. Thus, 1,25(OH)2D inhibits iFGF23 cleavage via VDR-mediated suppression of Furin expression, thereby providing a mechanism by which vitamin D can augment phosphaturic iFGF23 levels.

Indexed as

CalcitriolFurinAnimalsCell LineChromatin ImmunoprecipitationMiceVitamin DCalcitriolFurinVitamin DBone diseaseBone marrowEndocrinologyNephrology

Identifiers

PMID37681408
PMCPMC10544208
OpenAlexW4386523949

What OpenQuestion holds

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LicenceCC BY
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.