Evidence map›Paper›PMID 28886014›Full record

ArticlePloS one2017

Downregulation of autophagy is associated with severe ischemia-reperfusion-induced acute kidney injury in overexpressing C-reactive protein mice.

Ao Bian, Mingjun Shi, Brianna Flores, Nancy Gillings, Peng Li, Shirley Xiao Yan, Beth Levine, Changying Xing, Ming Chang Hu

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed, 1 pooled it
3.6field-weighted citation impact, top 6% 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

25 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Article
  5. Role of C-Reactive Protein in Kidney Diseases.Kidney diseases (Basel, Switzerland) · 2023
    Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Inflammatory stress in SARS-COV-2 associated Acute Kidney Injury.International journal of biological sciences · 2021
    Review
  12. Review
  13. Article
  14. The tripartite interaction of phosphate, autophagy, and αKlotho in health maintenance.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020
    Article
  15. Article
  16. Article
  17. Review
  18. Article
  19. Review
  20. Article
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

9 authors at 3 institutions in 2 countries.

Ao BianDepartment of Nephrology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
Mingjun ShiCharles and Jane Pak Center for Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center, Dallas, TX, United States of America.
Brianna FloresCharles and Jane Pak Center for Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center, Dallas, TX, United States of America.
Nancy GillingsCharles and Jane Pak Center for Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center, Dallas, TX, United States of America.
Peng LiDepartment of Nephrology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
Shirley Xiao YanDepartments of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, United States of America.
Beth LevineDepartments of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, United States of America.
Changying XingDepartment of Nephrology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
Ming Chang HuCharles and Jane Pak Center for Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center, Dallas, TX, United States of America.ORCID http://orcid.org/0000-0002-3235-8301
The University of Texas Southwestern Medical Center · USJiangsu Province Hospital · CNHoward Hughes Medical Institute · US

Funding

Klotho: Therapeutic Agent for Ischemia Reperfusion Induced Acute Kidney InjuryR01DK092461 · NIDDK · UT SOUTHWESTERN MEDICAL CENTER · PI HU, MING-CHANG · 2011 to 2021
$3.7M
Klotho and Phosphate in Chronic Kidney Disease: Pathogenesis and TherapeuticsR01DK091392 · NIDDK · UT SOUTHWESTERN MEDICAL CENTER · PI HU, MING-CHANG, MOE, ORSON W · 2011 to 2021
$3.2M
Beclin 1-Bcl-2 Interactions: Effects on AutophagyR01CA109618 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI LEVINE, BETH C · 2004 to 2014
$3.1M
NCI NIH HHS R01 CA109618NIDDK NIH HHS R01 DK091392NIDDK NIH HHS R01 DK092461
6 · The paper itself

Abstract

C-reactive protein (CRP), was recently reported to be closely associated with poor renal function in patients with acute kidney injury (AKI), but whether CRP is pathogenic or a mere biomarker in AKI remains largely unclear. Impaired autophagy is known to exacerbate renal ischemia-reperfusion injury (IRI). We examined whether the pathogenic role of CRP in AKI is associated with reduction of autophagy. We mated transgenic rabbit CRP over-expressing mice (Tg-CRP) with two autophagy reporter mouse lines, Tg-GFP-LC3 mice (LC3) and Tg-RFP-GFP-LC3 mice (RG-LC3) respectively to generate Tg-CRP-GFP-LC3 mice (PLC3) and Tg-CRP-RFP-GFP-LC3 mice (PRG-LC3). AKI was induced by IRI. Compared with LC3 mice, PLC3 mice developed more severe kidney damage after IRI. Renal tubules were isolated from LC3 mice at baseline for primary culture. OKP cells were transiently transfected with GFP-LC3 plasmid. CRP addition exacerbated lactate dehydrogenase release from both cell types. Immunoblots showed lower LC-3 II/I ratios and higher levels of p62, markers of reduced autophagy flux, in the kidneys of PLC3 mice compared to LC3 mice after IRI, and in primary cultured renal tubules and OKP cells treated with CRP and H2O2 compared to H2O2 alone. Immunohistochemistry showed much fewer LC-3 punctae, and electron microscopy showed fewer autophagosomes in kidneys of PLC3 mice compared to LC3 mice after IRI. Similarly, CRP addition reduced GFP-LC3 punctae induced by H2O2 in primary cultured proximal tubules and in GFP-LC3 plasmid transfected OKP cells. Rapamycin, an autophagy inducer, rescued impaired autophagy and reduced renal injury in vivo. In summary, it was suggested that CRP be more than mere biomarker in AKI, and render the kidney more susceptible to ischemic/oxidative injury, which is associated with down-regulating autophagy flux.

Indexed as

Gene ExpressionAcute Kidney InjuryAnimalsAutophagyBeclin-1C-Reactive ProteinDisease Models, AnimalEpithelial CellsHumansKidney TubulesMiceProtein BindingProto-Oncogene Proteins c-bcl-2RabbitsReperfusion InjurySeverity of Illness IndexBeclin-1C-Reactive ProteinProto-Oncogene Proteins c-bcl-2Sirolimus

Identifiers

PMID28886014
PMCPMC5590740
OpenAlexW2752672855

What OpenQuestion holds

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LicenceCC BY
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.