Evidence map›Paper›PMID 34473647›Full record

ArticleJCI insight2021

AMPK mediates regulation of glomerular volume and podocyte survival.

Khadija Banu, Qisheng Lin, John M Basgen, Marina Planoutene, Chengguo Wei, Anand C Reghuvaran, Xuefei Tian, Hongmei Shi, Felipe Garzon, Aitor Garzia and 15 more

Open access · goldAbstract read
In one paragraph

Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
2.4field-weighted citation impact, top 10% 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

17 citing papers in PubMed, 23 citations in OpenAlex.

  1. Review
  2. Article
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  5. Article
  6. Review
  7. Article
  8. Advancing mouse models for transplantation research.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2024
    Article
  9. Article
  10. Review
  11. Review
  12. Article
  13. Molecular pathways that drive diabetic kidney disease.The Journal of clinical investigation · 2023
    Review
  14. Article
  15. Review
  16. Review
  17. The Pathology Lesion Patterns of Podocytopathies: How and why?Frontiers in cell and developmental biology · 2022
    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

25 authors at 6 institutions in 2 countries.

Khadija BanuDivision of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Qisheng LinDivision of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
John M BasgenMorphometry and Stereology Laboratory, Charles R. Drew University of Medicine and Science, Los Angeles, California, USA.
Marina PlanouteneDivision of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Chengguo WeiDivision of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Anand C ReghuvaranDivision of Nephrology, Department of Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.
Xuefei TianDivision of Nephrology, Department of Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.
Hongmei ShiDivision of Nephrology, Department of Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.
Felipe GarzonDivision of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Aitor GarziaLaboratory of RNA Molecular Biology, The Rockefeller University, New York, New York, USA.
Nicholas ChunDivision of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Arun CumpelikDivision of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Andrew D SanteusanioDivision of Nephrology, Department of Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.
Weijia ZhangDivision of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Bhaskar DasDivision of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Fadi SalemDepartment of Pathology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Li LiDepartment of Pathology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Shuta IshibeDivision of Nephrology, Department of Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.
Lloyd G CantleyDivision of Nephrology, Department of Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.
Lewis KaufmanDivision of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Kevin V LemleyDepartment of Pediatrics, Children's Hospital Los Angeles, University of Southern California, Los Angeles, California, USA.
Zhaohui NiDepartment of Nephrology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
John Cijiang HeDivision of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Barbara MurphyDivision of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Madhav C MenonDivision of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Icahn School of Medicine at Mount Sinai · USYale University · USShanghai Jiao Tong University · CNMorpho (United States) · USRockefeller University · USUniversity of Southern California · US

Funding

Training Program in Clinical & Translationa Research in Human Glomerular DiseaseU54DK083912 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI HOLZMAN, LAWRENCE B. · 2009 to 2023
$20.3M
Renal Physiology and Phenotyping CoreP30DK079310 · NIDDK · YALE UNIVERSITY · PI PREISIG, PATRICIA A · 2008 to 2022
$16.8M
Macrophage Function in Kidney RepairR01DK093771 · NIDDK · YALE UNIVERSITY · PI LLOYD G CANTLEY · 2012 to 2026
$3.9M
Dichotomous roles of Shroom3 in Tubular cells and Podocytes in native and allograft kidneysR01DK122164 · NIDDK · YALE UNIVERSITY · PI Madhav C Menon · 2019 to 2026
$2.7M
NIDDK NIH HHS P30 DK079310NIDDK NIH HHS R01 DK093771NIDDK NIH HHS R01 DK122164NIDDK NIH HHS U54 DK083912
6 · The paper itself

Abstract

Herein, we report that Shroom3 knockdown, via Fyn inhibition, induced albuminuria with foot process effacement (FPE) without focal segmental glomerulosclerosis (FSGS) or podocytopenia. Interestingly, knockdown mice had reduced podocyte volumes. Human minimal change disease (MCD), where podocyte Fyn inactivation was reported, also showed lower glomerular volumes than FSGS. We hypothesized that lower glomerular volume prevented the progression to podocytopenia. To test this hypothesis, we utilized unilateral and 5/6th nephrectomy models in Shroom3-KD mice. Knockdown mice exhibited less glomerular and podocyte hypertrophy after nephrectomy. FYN-knockdown podocytes had similar reductions in podocyte volume, implying that Fyn was downstream of Shroom3. Using SHROOM3 or FYN knockdown, we confirmed reduced podocyte protein content, along with significantly increased phosphorylated AMPK, a negative regulator of anabolism. AMPK activation resulted from increased cytoplasmic redistribution of LKB1 in podocytes. Inhibition of AMPK abolished the reduction in glomerular volume and induced podocytopenia in mice with FPE, suggesting a protective role for AMPK activation. In agreement with this, treatment of glomerular injury models with AMPK activators restricted glomerular volume, podocytopenia, and progression to FSGS. Glomerular transcriptomes from MCD biopsies also showed significant enrichment of Fyn inactivation and Ampk activation versus FSGS glomeruli. In summary, we demonstrated the important role of AMPK in glomerular volume regulation and podocyte survival. Our data suggest that AMPK activation adaptively regulates glomerular volume to prevent podocytopenia in the context of podocyte injury.

Indexed as

Adenylate KinaseAdolescentAdultAgedAlbuminuriaAnimalsCell SizeCell SurvivalChildChild, PreschoolFemaleGene Knockdown TechniquesGlomerulonephritis, MembranousGlomerulosclerosis, Focal SegmentalHumansHypertrophyAdenylate KinaseFYN protein, humanFyn protein, mouseMicrofilament ProteinsProto-Oncogene Proteins c-fynShrm protein, mouseCell BiologyCytoskeletonMouse modelsNephrologyStructural biology

Identifiers

PMID34473647
PMCPMC8525649
OpenAlexW3197466860

What OpenQuestion holds

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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.