Evidence map›Paper›PMID 28873458›Full record

ArticlePloS one2017

Anti-fibrotic effects of valproic acid in experimental peritoneal fibrosis.

Elerson C Costalonga, Luiza J de Freitas, Deise da S P Aragone, Filipe M O Silva, Irene L Noronha

Open access · goldAbstract read
PubMed Full text at PMC Publisher
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 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.5field-weighted citation impact, top 18% 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

11 citing papers in PubMed, 29 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

5 authors at 1 institution in 1 country.

Elerson C CostalongaLaboratory of Cellular, Genetic, and Molecular Nephrology, Renal Division, University of São Paulo Medical School, São Paulo, Brazil.ORCID http://orcid.org/0000-0003-3282-9457
Luiza J de FreitasLaboratory of Cellular, Genetic, and Molecular Nephrology, Renal Division, University of São Paulo Medical School, São Paulo, Brazil.
Deise da S P AragoneLaboratory of Cellular, Genetic, and Molecular Nephrology, Renal Division, University of São Paulo Medical School, São Paulo, Brazil.
Filipe M O SilvaLaboratory of Cellular, Genetic, and Molecular Nephrology, Renal Division, University of São Paulo Medical School, São Paulo, Brazil.
Irene L NoronhaLaboratory of Cellular, Genetic, and Molecular Nephrology, Renal Division, University of São Paulo Medical School, São Paulo, Brazil.
Universidade de São Paulo · BR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundProgressive fibrous thickening of the peritoneal membrane is a complication of long-term peritoneal dialysis (PD). TGF-β/Smad pathway activation, inflammation, and neoangiogenesis play important roles in peritoneal membrane (PM) changes induced by PD. Recently, histone deacetilase inhibitors (HDACi) have shown anti-fibrotic and anti-inflammatory effects in different experimental models. These drugs prevent deacetylation of histones causing a loosen chromatin, which in turn induce the expression of some anti-fibrotic genes. In addition, acetylation may increase the activity of proteins involved in tissue fibrosis, such as Smad7. Here, we explored the effect of valproic acid (VPA), an HDACi, on the development of peritoneal fibrosis (PF) in rats.

methodsPF was induced by daily intraperitoneal injections of 0.1% chlorhexidine gluconate (CG) for 15 consecutive days. Male Wistar rats (250-300 g) were divided into 3 groups: CONTROL, control rats receiving only vehicle; PF, peritoneal fibrosis induced in rats; PF+VPA, rats with PF treated with VPA (300 mg/kg/day by gavage). PF was assessed by Masson's trichrome staining. Inflammation and fibrosis-associated factors were assessed by immunohistochemistry, immunofluorescence, multiplex analysis, and qPCR.

resultsTreatment with VPA significantly reduced PM thickness and the expression of myofibroblasts, besides preventing loss of ultrafiltration capacity of the PM. The upregulation of profibrotic factors (TGF-β, fibronectin, and Smad3) in the PF group was significantly ameliorated by VPA. VPA modulated the TGF/Smad pathway, inhibiting phosphorylated Smad3 expression and inducing an increased Smad7 expression in the FP+VPA group. The neoangiogenesis and the expression of proinflammatory cytokines (TNF-α, IL-1β, MCP-1) observed in the PF group was significantly reduced by VPA.

conclusionsOur results indicate that VPA suppressed experimental PF through modulation of the TGF-β/Smad pathway. Interestingly, VPA treatment induced a higher expression of antifibrotic factors, such as Smad7. These results suggest that VPA may represent a potential strategy for treating long term PD complications.

Indexed as

AnimalsBiological TransportBiomarkersBody WeightBone Morphogenetic Protein 7Calcium-Binding ProteinsCapillariesCell CountCytokinesFibronectinsGene Expression RegulationInflammationInflammation MediatorsMaleMyofibroblastsNeovascularization, PhysiologicBiomarkersBone Morphogenetic Protein 7Calcium-Binding ProteinsCytokinesFibronectinsFSP1 protein, ratInflammation MediatorsRNA, MessengerSmad ProteinsTransforming Growth Factor betaValproic AcidVascular Endothelial Growth Factor A

Identifiers

PMID28873458
PMCPMC5584960
OpenAlexW2752710142

What OpenQuestion holds

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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.