Evidence map›Paper›PMID 37726857›Full record

ArticleJournal of translational medicine2023

Brahma-related gene 1 acts as a profibrotic mediator and targeting it by micheliolide ameliorates peritoneal fibrosis.

Shuting Li, Congwei Luo, Sijia Chen, Yiyi Zhuang, Yue Ji, Yiqun Zeng, Yao Zeng, Xiaoyang He, Jing Xiao, Huizhen Wang and 3 more

Open access · goldAbstract read
In one paragraph

Article in Journal of translational medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.4field-weighted citation impact, top 19% 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

6 citing papers in PubMed, 9 citations in OpenAlex.

  1. Review
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  6. Review
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

13 authors at 3 institutions in 1 country.

Shuting Li *Department of Nephrology, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, China.
Congwei Luo *Department of Nephrology, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, China.
Sijia Chen *Department of Nephrology and Rheumatology, The First Hospital of Changsha, Changsha, China.
Yiyi ZhuangDepartment of Nephrology, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, China.
Yue JiDepartment of Nephrology, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, China.
Yiqun ZengDepartment of Nephrology, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, China.
Yao ZengDepartment of Nephrology, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, China.
Xiaoyang HeDepartment of Nephrology, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, China.
Jing XiaoDepartment of Nephrology, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, China.
Huizhen WangDepartment of Nephrology, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, China.
Xiaowen ChenDepartment of Nephrology, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, China. 573281676@qq.com.
Haibo LongDepartment of Nephrology, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, China. longhb1966@163.com.
Fenfen PengDepartment of Nephrology, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, China. doctorpff@163.com.
Zhujiang Hospital · CNSouthern Medical University · CNThe First Hospital of Changsha · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundProgressive peritoneal fibrosis is a worldwide public health concern impacting patients undergoing peritoneal dialysis (PD), yet there is no effective treatment. Our previous study revealed that a novel compound, micheliolide (MCL) inhibited peritoneal fibrosis in mice. However, its mechanism remains unclear. Brahma-related gene 1 (BRG1) is a key contributor to organ fibrosis, but its potential function in PD-related peritoneal fibrosis and the relationship between MCL and BRG1 remain unknown.

methodsThe effects of MCL on BRG1-induced fibrotic responses and TGF-β1-Smads pathway were examined in a mouse PD model and in vitro peritoneal mesothelial cells. To investigate the targeting mechanism of MCL on BRG1, coimmunoprecipitation, MCL-biotin pulldown, molecular docking and cellular thermal shift assay were performed.

resultsBRG1 was markedly elevated in a mouse PD model and in peritoneal mesothelial cells cultured in TGF-β1 or PD fluid condition. BRG1 overexpression in vitro augmented fibrotic responses and promoted TGF-β1-increased-phosphorylation of Smad2 and Smad3. Meanwhile, knockdown of BRG1 diminished TGF-β1-induced fibrotic responses and blocked TGF-β1-Smad2/3 pathway. MCL ameliorated BRG1 overexpression-induced peritoneal fibrosis and impeded TGF-β1-Smad2/3 signaling pathway both in a mouse PD model and in vitro. Mechanically, MCL impeded BRG1 from recognizing and attaching to histone H3 lysine 14 acetylation by binding to the asparagine (N1540) of BRG1, in thus restraining fibrotic responses and TGF-β1-Smad2/3 signaling pathway. After the mutation of N1540 to alanine (N1540A), MCL was unable to bind to BRG1 and thus, unsuccessful in suppressing BRG1-induced fibrotic responses and TGF-β1-Smad2/3 signaling pathway.

conclusionOur research indicates that BRG1 may be a crucial mediator in peritoneal fibrosis and MCL targeting N1540 residue of BRG1 may be a novel therapeutic strategy to combat PD-related peritoneal fibrosis.

Indexed as

Peritoneal DialysisPeritoneal FibrosisAnimalsDisease Models, AnimalDNA HelicasesMiceMolecular Docking SimulationNuclear ProteinsSesquiterpenes, GuaianeTranscription FactorsTransforming Growth Factor beta1DNA HelicasesmicheliolideNuclear ProteinsSesquiterpenes, GuaianeSmarca4 protein, mouseTranscription FactorsTransforming Growth Factor beta1BRG1MicheliolidePeritoneal dialysisPeritoneal fibrosisTGF-β1

Identifiers

PMID37726857
PMCPMC10510267
OpenAlexW4386844779

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.