Evidence map›Paper›PMID 25143942›Full record

ArticleBioMed research international2014

Upregulation of transglutaminase and ε (γ-glutamyl)-lysine in the Fisher-Lewis rat model of chronic allograft nephropathy.

Badri Shrestha, Imran Butt, Michelle Da Silva, Armando Sanchez-Lara, Bart Wagner, Andrew Raftery, Timothy Johnson, John Haylor

Open access · hybridAbstract read
In one paragraph

Article in BioMed research international, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.7field-weighted citation impact, top 31% 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

2 citing papers in PubMed, 7 citations in OpenAlex.

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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

8 authors at 2 institutions in 1 country.

Badri ShresthaDivision of Renal Transplantation, Sheffield Kidney Institute, Northern General Hospital, Herries Road, Sheffield S5 7AU, UK.ORCID 0000-0002-7309-7080
Imran ButtDivision of Renal Transplantation, Sheffield Kidney Institute, Northern General Hospital, Herries Road, Sheffield S5 7AU, UK.
Michelle Da SilvaAcademic Nephrology Unit, Medical School, University of Sheffield, Sheffield S10 2RX, UK.
Armando Sanchez-LaraAcademic Nephrology Unit, Medical School, University of Sheffield, Sheffield S10 2RX, UK.
Bart WagnerDivision of Renal Transplantation, Sheffield Kidney Institute, Northern General Hospital, Herries Road, Sheffield S5 7AU, UK.ORCID 0000-0003-1244-3063
Andrew RafteryDivision of Renal Transplantation, Sheffield Kidney Institute, Northern General Hospital, Herries Road, Sheffield S5 7AU, UK.
Timothy JohnsonAcademic Nephrology Unit, Medical School, University of Sheffield, Sheffield S10 2RX, UK.
John HaylorAcademic Nephrology Unit, Medical School, University of Sheffield, Sheffield S10 2RX, UK.ORCID 0000-0001-7385-1197
Northern General Hospital · GBUniversity of Sheffield · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundTissue transglutaminase (TG2), a cross-linking enzyme, modulates deposition of extracellular matrix protein in renal fibrosis. This study aimed to examine TG2 and its cross-link product ε(γ-glutamyl)-lysine in the Fisher-Lewis rat renal transplantation (RTx) model of chronic allograft nephropathy (CAN). MATERIALS AND

methodsLeft renal grafts from male Fisher and Lewis were transplanted into Lewis rats, generating allografts and isografts, respectively. Blood pressure, renal function, and proteinuria were monitored for up to 52 weeks. At termination, CAN was assessed in the renal tissue by light and electron microscopy, TG2 and ε(γ-glutamyl)-lysine by immunofluorescence, and the urinary ε(γ-glutamyl)-lysine by high performance liquid chromatography.

resultsCompared to the isograft, the allografts were hypertensive, proteinuric, and uraemic and developed CAN. Extracellular TG2 (glomerulus: 64.55 ± 17.61 versus 2.11 ± 0.17, P < 0.001; interstitium: 13.72 ± 1.62 versus 3.19 ± 0.44, P < 0.001), ε(γ-glutamyl)-lysine (glomerulus: 21.74 ± 2.71 versus 1.98 ± 0.37, P < 0.01; interstitium: 37.96 ± 17.06 versus 0.42 ± 0.11, P < 0.05), TG2 enzyme activity (1.09 ± 0.13 versus 0.41 ± 0.03 nmol/h/mg protein, P < 0.05), TG2 mRNA (20-fold rise), and urinary ε(γ-glutamyl)-lysine (534.2 ± 198.4 nmol/24 h versus 57.2 ± 4.1 nmol/24 h, P < 0.05) levels were significantly elevated in the allografts and showed a positive linear correlation with tubulointerstitial fibrosis.

conclusionCAN was associated with upregulation of renal TG2 pathway, which has a potential for pharmacological intervention. The elevated urinary ε(γ-glutamyl)-lysine, measured for the first time in RTx, is a potential biomarker of CAN.

Indexed as

Up-RegulationAllograftsAnimalsChronic DiseaseCross-Linking ReagentsDipeptidesDisease Models, AnimalFluorescent Antibody TechniqueGTP-Binding ProteinsKidney DiseasesKidney GlomerulusKidney TransplantationMaleProtein Glutamine gamma Glutamyltransferase 2Rats, Inbred F344Rats, Inbred LewCross-Linking ReagentsDipeptidesepsilon-(gamma-glutamyl)-lysineGTP-Binding ProteinsProtein Glutamine gamma Glutamyltransferase 2RNA, MessengerTgm2 protein, ratTransglutaminases

Identifiers

PMID25143942
PMCPMC4131109
OpenAlexW1993869265

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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.