Evidence map›Paper›PMID 36963615›Full record

ArticleMolecular metabolism2023

Calponin 2 harnesses metabolic reprogramming to determine kidney fibrosis.

Yuan Gui, Yuanyuan Wang, Zachary Palanza, Jack L Wang, Priya Gupta, Jianling Tao, Yi Qiao, Geneva Hargis, Donald L Kreutzer, Sheldon I Bastacky and 5 more

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

Article in Molecular metabolism, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed, 1 pooled it
3.7field-weighted citation impact, top 7% 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

15 citing papers in PubMed, 1 synthesis or guideline pooled it, 14 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Extracellular Matrix Control of Kidney Metabolism in Acute Kidney Injury and Repair.Journal of the American Society of Nephrology : JASN · 2026
    Article
  5. Article
  6. Article
  7. Review
  8. Review
  9. Article
  10. Review
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  12. Proteome characterization of liver-kidney comorbidity after microbial sepsis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024
    Article
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  14. Article
  15. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors at 5 institutions in 2 countries.

Yuan GuiDivision of Nephrology, Department of Medicine, University of Connecticut School of Medicine, Farmington, CT, 06030, USA.
Yuanyuan WangDivision of Nephrology, Department of Medicine, University of Connecticut School of Medicine, Farmington, CT, 06030, USA.
Zachary PalanzaDivision of Nephrology, Department of Medicine, University of Connecticut School of Medicine, Farmington, CT, 06030, USA.
Jack L WangDivision of Nephrology, Department of Medicine, University of Connecticut School of Medicine, Farmington, CT, 06030, USA.
Priya GuptaDivision of Nephrology, Department of Medicine, University of Connecticut School of Medicine, Farmington, CT, 06030, USA.
Jianling TaoDivision of Nephrology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, 94305, USA.
Yi QiaoDepartment of Surgery, University of Connecticut School of Medicine, Farmington, CT, 06030, USA.
Geneva HargisUniversity of Connecticut, School of Medicine, Farmington, CT, 06030, USA.
Donald L KreutzerDepartment of Surgery, University of Connecticut School of Medicine, Farmington, CT, 06030, USA.
Sheldon I BastackyDepartment of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15261, USA.
Yanbao YuDepartment of Chemistry & Biochemistry, University of Delaware, Newark, DE, 19716, USA.
Yanlin WangDivision of Nephrology, Department of Medicine, University of Connecticut School of Medicine, Farmington, CT, 06030, USA.
Silvia LiuDepartment of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15261, USA.
Haiyan FuState Key Laboratory of Organ Failure Research, National Clinical Research Center of Kidney Disease, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
Dong ZhouDivision of Nephrology, Department of Medicine, University of Connecticut School of Medicine, Farmington, CT, 06030, USA. Electronic address: dzhou@uchc.edu.
University of Connecticut · USUniversity of Pittsburgh · USNanfang Hospital · CNStanford University · USUniversity of Delaware · US

Funding

Single Nephron and MetabolomicsP30DK079307 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI CARATTINO, MARCELO DANIEL · 2008 to 2022
$13.4M
Importance of cell-matrix interactions in kidney repair after acute kidney injuryR01DK132059 · NIDDK · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · PI Dong Zhou · 2023 to 2026
$1.9M
Early and Transient Activation of Fibroblasts Promotes Tubule Repair after Acute Kidney InjuryK01DK116816 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI ZHOU, DONG · 2019 to 2021
$509k
The formation of kidney local microenvironment after acute kidney injury.R03DK128529 · NIDDK · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · PI ZHOU, DONG · 2021 to 2022
$246k
NIDDK NIH HHS K01 DK116816NIDDK NIH HHS P30 DK079307NIDDK NIH HHS R01 DK132059NIDDK NIH HHS R03 DK128529
6 · The paper itself

Abstract

objectiveIn the fibrotic kidneys, the extent of a formed deleterious microenvironment is determined by cellular mechanical forces. This process requires metabolism for energy. However, how cellular mechanics and metabolism are connected remains unclear.

methodsA multi-disciplinary approach was employed: the fibrotic kidney disease models were induced by renal ischemia-reperfusion injury and unilateral ureteral obstruction in Calponin 2 (CNN2) knockdown mice. Proteomics, bioinformatics, and in vivo and in vitro molecular experimental pathology studies were performed.

resultOur proteomics revealed that actin filament binding and cell metabolism are the two most dysregulated events in the fibrotic kidneys. As a prominent actin stabilizer, CNN2 was predominantly expressed in fibroblasts and pericytes. In CKD patients, CNN2 levels was markedly induced in blood. In mice, CNN2 knockdown preserves kidney function and alleviates fibrosis. Global proteomics profiled that CNN2 knockdown enhanced the activities of the key rate-limiting enzymes and regulators of fatty acid oxidation (FAO) in the diseased kidneys. Inhibiting carnitine palmitoyltransferase 1α in the FAO pathway resulted in lipid accumulation and extracellular matrix deposition in the fibrotic kidneys, which were restored after CNN2 knockdown. Bioinformatics and chromatin immunoprecipitation showed that CNN2 interactor, estrogen receptor 2 (ESR2), binds peroxisome proliferator-activated receptor-α (PPARα) to transcriptionally regulate FAO downstream target genes expression amid kidney fibrosis. In vitro, ESR2 knockdown repressed the mRNA levels of PPARα and the key genes in the FAO pathway. Conversely, activation of PPARα reduced CNN2-induced matrix inductions.

conclusionsOur results suggest that balancing cell mechanics and metabolism is crucial to develop therapeutic strategies to halt kidney fibrosis.

Indexed as

Calmodulin-Binding ProteinsKidney DiseasesAnimalsCalponinsFibrosisKidneyMiceMicrofilament ProteinsPPAR alphaCalmodulin-Binding ProteinsCalponinsCnn2 protein, mouseMicrofilament ProteinsPPAR alphaCalponin 2Chronic kidney diseaseESR2Fatty acid oxidationProteomics

Identifiers

PMID36963615
PMCPMC10090436
OpenAlexW4353047032

What OpenQuestion holds

Textmetadata
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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.