Evidence map›Paper›PMID 26671181›Full record

ArticleEndocrinology2016

Ablation of the Stimulatory G Protein α-Subunit in Renal Proximal Tubules Leads to Parathyroid Hormone-Resistance With Increased Renal Cyp24a1 mRNA Abundance and Reduced Serum 1,25-Dihydroxyvitamin D.

Yan Zhu, Qing He, Cumhur Aydin, Isabelle Rubera, Michel Tauc, Min Chen, Lee S Weinstein, Vladimir Marshansky, Harald Jüppner, Murat Bastepe

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

Article in Endocrinology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
0.8field-weighted citation impact, top 27% 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

8 citing papers in PubMed, 10 citations in OpenAlex.

  1. Physiopathology of Phosphate Disorders.Advances in kidney disease and health · 2023
    Review
  2. Article
  3. The regulation of FGF23 under physiological and pathophysiological conditions.Pflugers Archiv : European journal of physiology · 2022
    Review
  4. Dent disease: A window into calcium and phosphate transport.Journal of cellular and molecular medicine · 2019
    Review
  5. Review
  6. Article
  7. Article
  8. Review
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

10 authors at 5 institutions in 3 countries.

Yan ZhuEndocrine Unit (Z.Y., Q.H., C.A., H.J., M.B.), Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114; Department of Endodontics (C.A.), Gülhane Military Medical Academy, 06018 Ankara, Turkey; Faculty of Medicine (I.R., M.T.), Université de Nice Sophia Antipolis, 06107 Nice, France; Metabolic Diseases Branch (M.C., L.S.W.), National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892; Program in Membrane Biology (V.M.), Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114; Pediatric Nephrology Unit (H.J.), Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114.
Qing HeEndocrine Unit (Z.Y., Q.H., C.A., H.J., M.B.), Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114; Department of Endodontics (C.A.), Gülhane Military Medical Academy, 06018 Ankara, Turkey; Faculty of Medicine (I.R., M.T.), Université de Nice Sophia Antipolis, 06107 Nice, France; Metabolic Diseases Branch (M.C., L.S.W.), National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892; Program in Membrane Biology (V.M.), Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114; Pediatric Nephrology Unit (H.J.), Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114.
Cumhur AydinEndocrine Unit (Z.Y., Q.H., C.A., H.J., M.B.), Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114; Department of Endodontics (C.A.), Gülhane Military Medical Academy, 06018 Ankara, Turkey; Faculty of Medicine (I.R., M.T.), Université de Nice Sophia Antipolis, 06107 Nice, France; Metabolic Diseases Branch (M.C., L.S.W.), National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892; Program in Membrane Biology (V.M.), Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114; Pediatric Nephrology Unit (H.J.), Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114.
Isabelle RuberaEndocrine Unit (Z.Y., Q.H., C.A., H.J., M.B.), Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114; Department of Endodontics (C.A.), Gülhane Military Medical Academy, 06018 Ankara, Turkey; Faculty of Medicine (I.R., M.T.), Université de Nice Sophia Antipolis, 06107 Nice, France; Metabolic Diseases Branch (M.C., L.S.W.), National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892; Program in Membrane Biology (V.M.), Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114; Pediatric Nephrology Unit (H.J.), Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114.
Michel TaucEndocrine Unit (Z.Y., Q.H., C.A., H.J., M.B.), Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114; Department of Endodontics (C.A.), Gülhane Military Medical Academy, 06018 Ankara, Turkey; Faculty of Medicine (I.R., M.T.), Université de Nice Sophia Antipolis, 06107 Nice, France; Metabolic Diseases Branch (M.C., L.S.W.), National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892; Program in Membrane Biology (V.M.), Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114; Pediatric Nephrology Unit (H.J.), Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114.
Min ChenEndocrine Unit (Z.Y., Q.H., C.A., H.J., M.B.), Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114; Department of Endodontics (C.A.), Gülhane Military Medical Academy, 06018 Ankara, Turkey; Faculty of Medicine (I.R., M.T.), Université de Nice Sophia Antipolis, 06107 Nice, France; Metabolic Diseases Branch (M.C., L.S.W.), National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892; Program in Membrane Biology (V.M.), Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114; Pediatric Nephrology Unit (H.J.), Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114.
Lee S WeinsteinEndocrine Unit (Z.Y., Q.H., C.A., H.J., M.B.), Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114; Department of Endodontics (C.A.), Gülhane Military Medical Academy, 06018 Ankara, Turkey; Faculty of Medicine (I.R., M.T.), Université de Nice Sophia Antipolis, 06107 Nice, France; Metabolic Diseases Branch (M.C., L.S.W.), National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892; Program in Membrane Biology (V.M.), Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114; Pediatric Nephrology Unit (H.J.), Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114.
Vladimir MarshanskyEndocrine Unit (Z.Y., Q.H., C.A., H.J., M.B.), Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114; Department of Endodontics (C.A.), Gülhane Military Medical Academy, 06018 Ankara, Turkey; Faculty of Medicine (I.R., M.T.), Université de Nice Sophia Antipolis, 06107 Nice, France; Metabolic Diseases Branch (M.C., L.S.W.), National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892; Program in Membrane Biology (V.M.), Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114; Pediatric Nephrology Unit (H.J.), Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114.
Harald JüppnerEndocrine Unit (Z.Y., Q.H., C.A., H.J., M.B.), Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114; Department of Endodontics (C.A.), Gülhane Military Medical Academy, 06018 Ankara, Turkey; Faculty of Medicine (I.R., M.T.), Université de Nice Sophia Antipolis, 06107 Nice, France; Metabolic Diseases Branch (M.C., L.S.W.), National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892; Program in Membrane Biology (V.M.), Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114; Pediatric Nephrology Unit (H.J.), Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114.
Murat BastepeEndocrine Unit (Z.Y., Q.H., C.A., H.J., M.B.), Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114; Department of Endodontics (C.A.), Gülhane Military Medical Academy, 06018 Ankara, Turkey; Faculty of Medicine (I.R., M.T.), Université de Nice Sophia Antipolis, 06107 Nice, France; Metabolic Diseases Branch (M.C., L.S.W.), National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892; Program in Membrane Biology (V.M.), Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114; Pediatric Nephrology Unit (H.J.), Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114.
Massachusetts General Hospital · USHarvard University · USUniversité Côte d'Azur · FRNational Institute of Diabetes and Digestive and Kidney Diseases · USNational Institutes of Health · US

Funding

PTH/PTHRP RECEPTOR DEFECTS IN PSEUDOHYPOPARATHYROIDISMR01DK046718 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI JUEPPNER, HARALD W. · 1993 to 2024
$6.0M
Studies Of Pseudohypoparathyroidism And Related DisordersZIADK043302 · NIDDK · NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES · PI WEINSTEIN, LEE · 2009 to 2025
$5.8M
Role of the Gnas Gene in Metabolic RegulationZIADK043313 · NIDDK · NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES · PI WEINSTEIN, LEE · 2009 to 2025
$4.9M
XLas Relative to Gsa in Bone and Mineral Ion MetabolismR01DK073911 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI BASTEPE, MURAT · 2007 to 2020
$4.9M
Intramural NIH HHSNIDDK NIH HHS R01 DK046718NIDDK NIH HHS R01 DK073911NIDDK NIH HHS R01DK073911NIDDK NIH HHS R01DK46718
6 · The paper itself

Abstract

PTH regulates serum calcium, phosphate, and 1,25-dihydroxyvitamin D (1,25(OH)2D) levels by acting on bone and kidney. In renal proximal tubules (PTs), PTH inhibits reabsorption of phosphate and stimulates the synthesis of 1,25(OH)2D. The PTH receptor couples to multiple G proteins. We here ablated the α-subunit of the stimulatory G protein (Gsα) in mouse PTs by using Cre recombinase driven by the promoter of type-2 sodium-glucose cotransporter (Gsα(Sglt2KO) mice). Gsα(Sglt2KO) mice were normophosphatemic but displayed, relative to controls, hypocalcemia (1.19 ±0.01 vs 1.23 ±0.01 mmol/L; P < .05), reduced serum 1,25(OH)2D (59.3 ±7.0 vs 102.5 ±12.2 pmol/L; P < .05), and elevated serum PTH (834 ±133 vs 438 ±59 pg/mL; P < .05). PTH-induced elevation in urinary cAMP excretion was blunted in Gsα(Sglt2KO) mice (2- vs 4-fold over baseline in controls; P < .05). Relative to baseline in controls, PTH-induced reduction in serum phosphate tended to be blunted in Gsα(Sglt2KO) mice (-0.39 ±0.33 vs -1.34 ±0.36 mg/dL; P = .07). Gsα(Sglt2KO) mice showed elevated renal vitamin D 24-hydroxylase and bone fibroblast growth factor-23 (FGF23) mRNA abundance (∼3.4- and ∼11-fold over controls, respectively; P < .05) and tended to have elevated serum FGF23 (829 ±76 vs 632 ±60 pg/mL in controls; P = .07). Heterozygous mice having constitutive ablation of the maternal Gsα allele (E1(m-/+)) (model of pseudohypoparathyroidism type-Ia), in which Gsα levels in PT are reduced, also exhibited elevated serum FGF23 (474 ±20 vs 374 ±27 pg/mL in controls; P < .05). Our findings indicate that Gsα is required in PTs for suppressing renal vitamin D 24-hydroxylase mRNA levels and for maintaining normal serum 1,25(OH)2D.

Indexed as

AnimalsDisease Models, AnimalDown-RegulationDrug ResistanceFemaleFibroblast Growth Factor-23GTP-Binding Protein alpha SubunitsKidney Tubules, ProximalMaleMiceMice, KnockoutParathyroid HormonePseudopseudohypoparathyroidismRNA, MessengerUp-RegulationVitamin D1,25-dihydroxyvitamin DCyp24a1 protein, mouseFgf23 protein, mouseFibroblast Growth Factor-23GTP-Binding Protein alpha SubunitsParathyroid HormoneRNA, MessengerVitamin DVitamin D3 24-Hydroxylase

Identifiers

PMID26671181
PMCPMC4733111
OpenAlexW2196611905

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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.