Evidence map›Paper›PMID 29889103›Full record

ArticleThe Journal of clinical investigation2018

SGK1 induces vascular smooth muscle cell calcification through NF-κB signaling.

Jakob Voelkl, Trang Td Luong, Rashad Tuffaha, Katharina Musculus, Tilman Auer, Xiaoming Lian, Christoph Daniel, Daniel Zickler, Beate Boehme, Michael Sacherer and 8 more

Open access · greenAbstract read
In one paragraph

Article in The Journal of clinical investigation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
92citing papers in PubMed, 1 pooled it
8.7field-weighted citation impact, top 1% 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

92 citing papers in PubMed, 1 synthesis or guideline pooled it, 170 citations in OpenAlex.

  1. Pooled it
  2. Review
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  8. Article
  9. Considerations in the Use of Mouse Models of Vascular and Valvular Calcification.Arteriosclerosis, thrombosis, and vascular biology · 2026
    Review
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  13. TGFβ signaling regulates the response of the skeleton to phosphate.bioRxiv : the preprint server for biology · 2025
    Article
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  15. Review
  16. Article
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32 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

18 authors at 9 institutions in 2 countries.

Jakob VoelklCharité - Universitätsmedizin Berlin, Department of Internal Medicine and Cardiology, Berlin, Germany.
Trang Td LuongCharité - Universitätsmedizin Berlin, Department of Internal Medicine and Cardiology, Berlin, Germany.
Rashad TuffahaDepartment of Physiology I, Eberhard Karls University, Tübingen, Germany.
Katharina MusculusDepartment of Physiology I, Eberhard Karls University, Tübingen, Germany.
Tilman AuerDepartment of Physiology I, Eberhard Karls University, Tübingen, Germany.
Xiaoming LianCharité - Universitätsmedizin Berlin, Department of Nephrology and Medical Intensive Care, Berlin, Germany.
Christoph DanielDepartment of Pathology, Universität Erlangen-Nürnberg, Erlangen, Germany.
Daniel ZicklerCharité - Universitätsmedizin Berlin, Department of Nephrology and Medical Intensive Care, Berlin, Germany.
Beate BoehmeCharité - Universitätsmedizin Berlin, Department of Internal Medicine and Cardiology, Berlin, Germany.
Michael SachererDepartment of Internal Medicine, Division of Cardiology, Medical University of Graz, Graz, Austria.
Bernhard MetzlerUniversity Clinic of Internal Medicine III, Cardiology and Angiology, Medical University of Innsbruck, Innsbruck, Austria.
Dietmar KuhlInstitute for Molecular and Cellular Cognition, Center for Molecular Neurobiology Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Maik GollaschCharité - Universitätsmedizin Berlin, Department of Nephrology and Medical Intensive Care, Berlin, Germany.
Kerstin AmannDepartment of Pathology, Universität Erlangen-Nürnberg, Erlangen, Germany.
Dominik N MüllerDZHK (German Centre for Cardiovascular Research), partner site Berlin, Berlin, Germany.
Burkert PieskeCharité - Universitätsmedizin Berlin, Department of Internal Medicine and Cardiology, Berlin, Germany.
Florian LangDepartment of Physiology I, Eberhard Karls University, Tübingen, Germany.
Ioana AlesutanCharité - Universitätsmedizin Berlin, Department of Internal Medicine and Cardiology, Berlin, Germany.
Charité - Universitätsmedizin Berlin · DEUniversity of Tübingen · DEFriedrich-Alexander-Universität Erlangen-Nürnberg · DEGerman Centre for Cardiovascular Research · DEDeutsches Herzzentrum der Charité · DEInnsbruck Medical University · ATMax Delbrück Center · DEMedical University of Graz · ATUniversität Hamburg · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Medial vascular calcification, associated with enhanced mortality in chronic kidney disease (CKD), is fostered by osteo-/chondrogenic transdifferentiation of vascular smooth muscle cells (VSMCs). Here, we describe that serum- and glucocorticoid-inducible kinase 1 (SGK1) was upregulated in VSMCs under calcifying conditions. In primary human aortic VSMCs, overexpression of constitutively active SGK1S422D, but not inactive SGK1K127N, upregulated osteo-/chondrogenic marker expression and activity, effects pointing to increased osteo-/chondrogenic transdifferentiation. SGK1S422D induced nuclear translocation and increased transcriptional activity of NF-κB. Silencing or pharmacological inhibition of IKK abrogated the osteoinductive effects of SGK1S422D. Genetic deficiency, silencing, and pharmacological inhibition of SGK1 dissipated phosphate-induced calcification and osteo-/chondrogenic transdifferentiation of VSMCs. Aortic calcification, stiffness, and osteo-/chondrogenic transdifferentiation in mice following cholecalciferol overload were strongly reduced by genetic knockout or pharmacological inhibition of Sgk1 by EMD638683. Similarly, Sgk1 deficiency blunted vascular calcification in apolipoprotein E-deficient mice after subtotal nephrectomy. Treatment of human aortic smooth muscle cells with serum from uremic patients induced osteo-/chondrogenic transdifferentiation, effects ameliorated by EMD638683. These observations identified SGK1 as a key regulator of vascular calcification. SGK1 promoted vascular calcification, at least partly, via NF-κB activation. Inhibition of SGK1 may, thus, reduce the burden of vascular calcification in CKD.

Indexed as

AnimalsBenzamidesCells, CulturedCell TransdifferentiationChondrogenesisDisease Models, AnimalGene Expression RegulationHumansHydrazinesImmediate-Early ProteinsMiceMice, Inbred C57BLMice, KnockoutMice, Knockout, ApoEMyocytes, Smooth MuscleNF-kappa BBenzamidesEMD 638683HydrazinesImmediate-Early ProteinsNF-kappa BProtein Kinase InhibitorsProtein Serine-Threonine KinasesSerum-Glucocorticoid Regulated KinasesCardiovascular diseaseCell BiologyChronic kidney diseaseNF-kappaBVascular Biology

Identifiers

PMID29889103
PMCPMC6025998
OpenAlexW2807672443

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.