Evidence map›Paper›PMID 27467172›Full record

ArticlePloS one2016

Heparanase: A Potential New Factor Involved in the Renal Epithelial Mesenchymal Transition (EMT) Induced by Ischemia/Reperfusion (I/R) Injury.

Valentina Masola, Gianluigi Zaza, Giovanni Gambaro, Maurizio Onisto, Gloria Bellin, Gisella Vischini, Iyad Khamaysi, Ahmad Hassan, Shadi Hamoud, Omri Nativ and 4 more

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
6.3field-weighted citation impact, top 3% 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

27 citing papers in PubMed, 61 citations in OpenAlex.

  1. Review
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  14. Endothelial Glycocalyx as a Regulator of Fibrotic Processes.International journal of molecular sciences · 2021
    Review
  15. Review
  16. Review
  17. Heparanase and the hallmarks of cancer.Journal of translational medicine · 2020
    Review
  18. Review
  19. Sirtuin 1 and endothelial glycocalyx.Pflugers Archiv : European journal of physiology · 2020
    Review
  20. Heparanase in Acute Kidney Injury.Advances in experimental medicine and biology · 2020
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 5 institutions in 2 countries.

Valentina MasolaRenal Unit, Department of Medicine, Verona, Italy.
Gianluigi ZazaRenal Unit, Department of Medicine, Verona, Italy.
Giovanni GambaroRenal Unit, Columbus-Gemelli Hospital, Catholic University of the Sacred Heart, Roma, Italy.
Maurizio OnistoUniversity of Padova, Department of Biomedical Sciences Padova, Padova, Italy.
Gloria BellinRenal Unit, Department of Medicine, Verona, Italy.
Gisella VischiniRenal Unit, Columbus-Gemelli Hospital, Catholic University of the Sacred Heart, Roma, Italy.
Iyad KhamaysiGastroenterology, Rambam Health Care Campus, Haifa, Israel.
Ahmad HassanInternal Medicine A, Rambam Health Care Campus, Haifa, Israel.
Shadi HamoudInternal Medicine E, Rambam Health Care Campus, Haifa, Israel.
Omri NativDepartment of Physiology and Biophysics, The Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel.
Samuel HeymanDepartment of Internal Medicine, Hadassah Medical Center, Jerusalem, Israel.
Antonio LupoRenal Unit, Department of Medicine, Verona, Italy.
Israel VlodavskyCancer and Vascular Biology Research Center, Rappaport Faculty of Medicine, Technion, Haifa, Israel.
Zaid AbassiDepartment of Physiology and Biophysics, The Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel.
Rambam Health Care Campus · ILUniversity of Verona · ITUniversità Cattolica del Sacro Cuore · ITHadassah Medical Center · ILUniversity of Padua · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundIschemia/reperfusion (I/R) is an important cause of acute renal failure and delayed graft function, and it may induce chronic renal damage by activating epithelial to mesenchymal transition (EMT) of renal tubular cells. Heparanase (HPSE), an endoglycosidase that regulates FGF-2 and TGFβ-induced EMT, may have an important role. Therefore, aim of this study was to evaluate its role in the I/R-induced renal pro-fibrotic machinery by employing in vitro and in vivo models.

methodsWild type (WT) and HPSE-silenced renal tubular cells were subjected to hypoxia and reoxygenation in the presence or absence of SST0001, an inhibitor of HPSE. In vivo, I/R injury was induced by bilateral clamping of renal arteries for 30 min in transgenic mice over-expressing HPSE (HPA-tg) and in their WT littermates. Mice were sacrificed 48 and 72 h after I/R. Gene and protein EMT markers (α-SMA, VIM and FN) were evaluated by bio-molecular and histological methodologies.

resultsIn vitro: hypoxia/reoxygenation (H/R) significantly increased the expression of EMT-markers in WT, but not in HPSE-silenced tubular cells. Notably, EMT was prevented in WT cells by SST0001 treatment. In vivo: I/R induced a remarkable up-regulation of EMT markers in HPA-tg mice after 48-72 h. Noteworthy, these effects were absent in WT animals.

conclusionsIn conclusion, our results add new insights towards understanding the renal biological mechanisms activated by I/R and they demonstrate, for the first time, that HPSE is a pivotal factor involved in the onset and development of I/R-induced EMT. It is plausible that in future the inhibition of this endoglycosidase may represent a new therapeutic approach to minimize/prevent fibrosis and slow down chronic renal disease progression in native and transplanted kidneys.

Indexed as

Epithelial-Mesenchymal TransitionAnimalsCell LineGlucuronidaseHeparanaseHumansKidneyKidney Tubules, ProximalMaleMiceMice, Inbred BALB CReperfusion InjuryGlucuronidaseHeparanase

Identifiers

PMID27467172
PMCPMC4965068
OpenAlexW2483114286

What OpenQuestion holds

Textmetadata
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.