Evidence map›Paper›PMID 26974005›Full record

ArticleEndocrinology2016

GATA4 Regulates Blood-Testis Barrier Function and Lactate Metabolism in Mouse Sertoli Cells.

Anja Schrade, Antti Kyrönlahti, Oyediran Akinrinade, Marjut Pihlajoki, Simon Fischer, Verena Martinez Rodriguez, Kerstin Otte, Vidya Velagapudi, Jorma Toppari, David B Wilson and 1 more

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 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
7.0field-weighted citation impact, top 4% 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

28 citing papers in PubMed, 56 citations in OpenAlex.

  1. Article
  2. Article
  3. COPS5 is Essential for Sertoli Cell Function and Male Fertility in Mice.bioRxiv : the preprint server for biology · 2025
    Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Review
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  13. In Vitro and In Vivo Models for Drug Transport Across the Blood-Testis Barrier.Drug metabolism and disposition: the biological fate of chemicals · 2023
    Review
  14. Article
  15. Article
  16. Article
  17. Review
  18. 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

11 authors at 5 institutions in 3 countries.

Anja SchradeChildren's Hospital (A.S., A.K., O.A., M.P., M.H.), University of Helsinki and Helsinki University Central Hospital, Helsinki 00014, Finland; Institute of Applied Biotechnology (S.F., K.O.), University of Applied Sciences Biberach, Biberach 88400, Germany; Metabolomics Unit (V.V.), Institute for Molecular Medicine Finland, University of Helsinki 00014, Helsinki, Finland; Departments of Physiology and Pediatrics (J.T.), University of Turku and Turku University Hospital, Turku 20520, Finland; and Departments of Pediatrics (A.S., V.M.R., D.B.W., M.H.) and Developmental Biology (D.B.W.), Washington University, St Louis, Missouri 63110.
Antti KyrönlahtiChildren's Hospital (A.S., A.K., O.A., M.P., M.H.), University of Helsinki and Helsinki University Central Hospital, Helsinki 00014, Finland; Institute of Applied Biotechnology (S.F., K.O.), University of Applied Sciences Biberach, Biberach 88400, Germany; Metabolomics Unit (V.V.), Institute for Molecular Medicine Finland, University of Helsinki 00014, Helsinki, Finland; Departments of Physiology and Pediatrics (J.T.), University of Turku and Turku University Hospital, Turku 20520, Finland; and Departments of Pediatrics (A.S., V.M.R., D.B.W., M.H.) and Developmental Biology (D.B.W.), Washington University, St Louis, Missouri 63110.
Oyediran AkinrinadeChildren's Hospital (A.S., A.K., O.A., M.P., M.H.), University of Helsinki and Helsinki University Central Hospital, Helsinki 00014, Finland; Institute of Applied Biotechnology (S.F., K.O.), University of Applied Sciences Biberach, Biberach 88400, Germany; Metabolomics Unit (V.V.), Institute for Molecular Medicine Finland, University of Helsinki 00014, Helsinki, Finland; Departments of Physiology and Pediatrics (J.T.), University of Turku and Turku University Hospital, Turku 20520, Finland; and Departments of Pediatrics (A.S., V.M.R., D.B.W., M.H.) and Developmental Biology (D.B.W.), Washington University, St Louis, Missouri 63110.
Marjut PihlajokiChildren's Hospital (A.S., A.K., O.A., M.P., M.H.), University of Helsinki and Helsinki University Central Hospital, Helsinki 00014, Finland; Institute of Applied Biotechnology (S.F., K.O.), University of Applied Sciences Biberach, Biberach 88400, Germany; Metabolomics Unit (V.V.), Institute for Molecular Medicine Finland, University of Helsinki 00014, Helsinki, Finland; Departments of Physiology and Pediatrics (J.T.), University of Turku and Turku University Hospital, Turku 20520, Finland; and Departments of Pediatrics (A.S., V.M.R., D.B.W., M.H.) and Developmental Biology (D.B.W.), Washington University, St Louis, Missouri 63110.
Simon FischerChildren's Hospital (A.S., A.K., O.A., M.P., M.H.), University of Helsinki and Helsinki University Central Hospital, Helsinki 00014, Finland; Institute of Applied Biotechnology (S.F., K.O.), University of Applied Sciences Biberach, Biberach 88400, Germany; Metabolomics Unit (V.V.), Institute for Molecular Medicine Finland, University of Helsinki 00014, Helsinki, Finland; Departments of Physiology and Pediatrics (J.T.), University of Turku and Turku University Hospital, Turku 20520, Finland; and Departments of Pediatrics (A.S., V.M.R., D.B.W., M.H.) and Developmental Biology (D.B.W.), Washington University, St Louis, Missouri 63110.
Verena Martinez RodriguezChildren's Hospital (A.S., A.K., O.A., M.P., M.H.), University of Helsinki and Helsinki University Central Hospital, Helsinki 00014, Finland; Institute of Applied Biotechnology (S.F., K.O.), University of Applied Sciences Biberach, Biberach 88400, Germany; Metabolomics Unit (V.V.), Institute for Molecular Medicine Finland, University of Helsinki 00014, Helsinki, Finland; Departments of Physiology and Pediatrics (J.T.), University of Turku and Turku University Hospital, Turku 20520, Finland; and Departments of Pediatrics (A.S., V.M.R., D.B.W., M.H.) and Developmental Biology (D.B.W.), Washington University, St Louis, Missouri 63110.
Kerstin OtteChildren's Hospital (A.S., A.K., O.A., M.P., M.H.), University of Helsinki and Helsinki University Central Hospital, Helsinki 00014, Finland; Institute of Applied Biotechnology (S.F., K.O.), University of Applied Sciences Biberach, Biberach 88400, Germany; Metabolomics Unit (V.V.), Institute for Molecular Medicine Finland, University of Helsinki 00014, Helsinki, Finland; Departments of Physiology and Pediatrics (J.T.), University of Turku and Turku University Hospital, Turku 20520, Finland; and Departments of Pediatrics (A.S., V.M.R., D.B.W., M.H.) and Developmental Biology (D.B.W.), Washington University, St Louis, Missouri 63110.
Vidya VelagapudiChildren's Hospital (A.S., A.K., O.A., M.P., M.H.), University of Helsinki and Helsinki University Central Hospital, Helsinki 00014, Finland; Institute of Applied Biotechnology (S.F., K.O.), University of Applied Sciences Biberach, Biberach 88400, Germany; Metabolomics Unit (V.V.), Institute for Molecular Medicine Finland, University of Helsinki 00014, Helsinki, Finland; Departments of Physiology and Pediatrics (J.T.), University of Turku and Turku University Hospital, Turku 20520, Finland; and Departments of Pediatrics (A.S., V.M.R., D.B.W., M.H.) and Developmental Biology (D.B.W.), Washington University, St Louis, Missouri 63110.
Jorma ToppariChildren's Hospital (A.S., A.K., O.A., M.P., M.H.), University of Helsinki and Helsinki University Central Hospital, Helsinki 00014, Finland; Institute of Applied Biotechnology (S.F., K.O.), University of Applied Sciences Biberach, Biberach 88400, Germany; Metabolomics Unit (V.V.), Institute for Molecular Medicine Finland, University of Helsinki 00014, Helsinki, Finland; Departments of Physiology and Pediatrics (J.T.), University of Turku and Turku University Hospital, Turku 20520, Finland; and Departments of Pediatrics (A.S., V.M.R., D.B.W., M.H.) and Developmental Biology (D.B.W.), Washington University, St Louis, Missouri 63110.
David B WilsonChildren's Hospital (A.S., A.K., O.A., M.P., M.H.), University of Helsinki and Helsinki University Central Hospital, Helsinki 00014, Finland; Institute of Applied Biotechnology (S.F., K.O.), University of Applied Sciences Biberach, Biberach 88400, Germany; Metabolomics Unit (V.V.), Institute for Molecular Medicine Finland, University of Helsinki 00014, Helsinki, Finland; Departments of Physiology and Pediatrics (J.T.), University of Turku and Turku University Hospital, Turku 20520, Finland; and Departments of Pediatrics (A.S., V.M.R., D.B.W., M.H.) and Developmental Biology (D.B.W.), Washington University, St Louis, Missouri 63110.
Markku HeikinheimoChildren's Hospital (A.S., A.K., O.A., M.P., M.H.), University of Helsinki and Helsinki University Central Hospital, Helsinki 00014, Finland; Institute of Applied Biotechnology (S.F., K.O.), University of Applied Sciences Biberach, Biberach 88400, Germany; Metabolomics Unit (V.V.), Institute for Molecular Medicine Finland, University of Helsinki 00014, Helsinki, Finland; Departments of Physiology and Pediatrics (J.T.), University of Turku and Turku University Hospital, Turku 20520, Finland; and Departments of Pediatrics (A.S., V.M.R., D.B.W., M.H.) and Developmental Biology (D.B.W.), Washington University, St Louis, Missouri 63110.
Washington University in St. Louis · USHelsinki University Hospital · FIUniversity of Applied Sciences Biberach · DEFinland University · FIUniversity of Turku · FI

Funding

Washington University DDRCC Supplemental Equipment RequestP30DK052574 · NIDDK · WASHINGTON UNIVERSITY · PI Nicholas O. Davidson · 2000 to 2026
$30.8M
Regulation of Steroidogenic Cell Differentiation in the MouseR01DK075618 · NIDDK · WASHINGTON UNIVERSITY · PI WILSON, DAVID B · 2007 to 2011
$1.4M
NIDDK NIH HHS P30 DK052574NIDDK NIH HHS R01 DK075618
6 · The paper itself

Abstract

Conditional deletion of Gata4 in Sertoli cells (SCs) of adult mice has been shown to increase permeability of the blood-testis barrier (BTB) and disrupt spermatogenesis. To gain insight into the molecular underpinnings of these phenotypic abnormalities, we assessed the impact of Gata4 gene silencing in cell culture models. Microarray hybridization identified genes dysregulated by siRNA-mediated inhibition of Gata4 in TM4 cells, an immortalized mouse SC line. Differentially expressed genes were validated by quantitative RT-PCR analysis of primary cultures of Gata4(flox/flox) mouse SCs that had been subjected to cre-mediated recombination in vitro. Depletion of GATA4 in TM4 cells and primary SCs was associated with altered expression of genes involved in key facets of BTB maintenance, including tight/adherens junction formation (Tjp1, Cldn12, Vcl, Tnc, Csk) and extracellular matrix reorganization (Lamc1, Col4a1, Col4a5, Mmp10, Mmp23, Timp2). Western blotting and immunocytochemistry demonstrated reduced levels of tight junction protein-1, a prototypical tight junction protein, in GATA4-depleted cells. These changes were accompanied by a loss of morphologically recognizable junctional complexes and a decline in epithelial membrane resistance. Furthermore, Gata4 gene silencing was associated with altered expression of Hk1, Gpi1, Pfkp, Pgam1, Gls2, Pdk3, Pkd4, and Ldhb, genes regulating the production of lactate, a key nutrient that SCs provide to developing germ cells. Comprehensive metabolomic profiling demonstrated impaired lactate production in GATA4-deficient SCs. We conclude that GATA4 plays a pivotal role in the regulation of BTB function and lactate metabolism in mouse SCs.

Indexed as

AnimalsBlood-Testis BarrierBlotting, WesternCollagen Type IVGATA4 Transcription FactorImmunohistochemistryLactatesLamininMaleMatrix Metalloproteinase 10Matrix Metalloproteinases, Membrane-AssociatedMiceRNA, Small InterferingSertoli CellsSpermatogenesisTestisCol4a1 protein, mouseCol4a5 protein, mouseCollagen Type IVGata4 protein, mouseGATA4 Transcription FactorLactatesLamininlaminin gamma 1Matrix Metalloproteinase 10Matrix Metalloproteinases, Membrane-AssociatedMmp24 protein, mouseRNA, Small InterferingTjp1 protein, mouseZonula Occludens-1 Protein

Identifiers

PMID26974005
PMCPMC4891789
OpenAlexW2297111965

What OpenQuestion holds

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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.