Evidence map›Paper›PMID 34769294›Full record

ArticleInternational journal of molecular sciences2021

The Fibrotic Effects of TMAO on Human Renal Fibroblasts Is Mediated by NLRP3, Caspase-1 and the PERK/Akt/mTOR Pathway.

Stefania Kapetanaki, Ashok Kumar Kumawat, Katarina Persson, Isak Demirel

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

Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
51citing papers in PubMed, 1 pooled it
5.7field-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

51 citing papers in PubMed, 1 synthesis or guideline pooled it, 72 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

4 authors at 2 institutions in 1 country.

Stefania KapetanakiSchool of Medical Sciences, Campus USÖ, Örebro University, 701 82 Örebro, Sweden.
Ashok Kumar KumawatSchool of Medical Sciences, Campus USÖ, Örebro University, 701 82 Örebro, Sweden.
Katarina PerssonSchool of Medical Sciences, Campus USÖ, Örebro University, 701 82 Örebro, Sweden.
Isak DemirelSchool of Medical Sciences, Campus USÖ, Örebro University, 701 82 Örebro, Sweden.
Örebro University · SEKarolinska University Hospital · SE

Funding

Faculty of Medicine and Health at Örebro University
6 · The paper itself

Abstract

Trimethylamine N-oxide (TMAO), a product of gut microbiota metabolism, has previously been shown to be implicated in chronic kidney disease. A high TMAO-containing diet has been found to cause tubulointerstitial renal fibrosis in mice. However, today there are no data linking specific molecular pathways with the effect of TMAO on human renal fibrosis. The aim of this study was to investigate the fibrotic effects of TMAO on renal fibroblasts and to elucidate the molecular pathways involved. We found that TMAO promoted renal fibroblast activation and fibroblast proliferation via the PERK/Akt/mTOR pathway, NLRP3, and caspase-1 signaling. We also found that TMAO increased the total collagen production from renal fibroblasts via the PERK/Akt/mTOR pathway. However, TMAO did not induce fibronectin or TGF-β1 release from renal fibroblasts. We have unraveled that the PERK/Akt/mTOR pathway, NLRP3, and caspase-1 mediates TMAO's fibrotic effect on human renal fibroblasts. Our results can pave the way for future research to further clarify the molecular mechanism behind TMAO's effects and to identify novel therapeutic targets in the context of chronic kidney disease.

Indexed as

Caspase 1Cell LineCell ProliferationCollageneIF-2 KinaseFibroblastsFibrosisGene Expression RegulationHumansKidneyMethylaminesModels, BiologicalNLR Family, Pyrin Domain-Containing 3 ProteinProto-Oncogene Proteins c-aktSignal TransductionTOR Serine-Threonine KinasesAKT1 protein, humanCaspase 1CollagenEIF2AK3 protein, humaneIF-2 KinaseMethylaminesMTOR protein, humanNLR Family, Pyrin Domain-Containing 3 ProteinNLRP3 protein, humanProto-Oncogene Proteins c-aktTOR Serine-Threonine Kinasestrimethyloxaminechronic kidney diseasecollagenproliferationrenal fibroblastsTMAO

Identifiers

PMID34769294
PMCPMC8584593
OpenAlexW3210162226

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.