Evidence map›Paper›PMID 34430599›Full record

ArticleAnnals of translational medicine2021

TGR5 protects against cholestatic liver disease via suppressing the NF-κB pathway and activating the Nrf2/HO-1 pathway.

Haojun Yang, Fengyong Luo, Yi Wei, Yuwen Jiao, Jun Qian, Shuai Chen, Yu Gong, Liming Tang

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

Article in Annals of translational medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
3.0field-weighted citation impact, top 8% 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

29 citing papers in PubMed, 33 citations in OpenAlex.

  1. Review
  2. Expanding bile acid diversityNatural product reports · 2026
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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 3 institutions in 1 country.

Haojun YangGastrointestinal Surgery Department, The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, Changzhou, China.
Fengyong LuoSchool of Graduate, Dalian Medical University, Dalian, China.
Yi WeiGastrointestinal Surgery Department, The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, Changzhou, China.
Yuwen JiaoGastrointestinal Surgery Department, The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, Changzhou, China.
Jun QianGastrointestinal Surgery Department, The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, Changzhou, China.
Shuai ChenGastrointestinal Surgery Department, The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, Changzhou, China.
Yu GongGastrointestinal Surgery Department, The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, Changzhou, China.
Liming TangGastrointestinal Surgery Department, The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, Changzhou, China.
Changzhou No.2 People's Hospital · CNNanjing Medical University · CNDalian Medical University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundCharacterized by the presence of inflammation, fibrosis, and bile duct proliferation, cholestatic liver disease (CLD) affects people of all age groups. Takeda G-protein-coupled receptor (TGR5) has been implicated in the suppression of inflammation via toll-like receptor 4 (TLR4) and nuclear factor kappa B (NF-κB). Kupffer cells and their M1 polarization play important roles in inflammation and cholestatic liver injury via production of pro-inflammatory cytokines. Nevertheless, the function of TGR5 signaling in CLD is largely unknown.

methodsWe conducted liver tissue experiments, animal experiments, serum marker testing, liver histology analysis, Kupffer cell experiments, RNA extraction and Real-time PCR, western blotting, evaluation of ROS production by flow cytometry and statistical differences were analyzed by student

resultsWe found that serum bile acid (BA) and TGR5 levels were elevated in patients with cholestasis cirrhosis. Knockout of TGR5 in animals significantly increased bile duct ligation (BDL)-caused liver injury through increasing oxidative stress, promoting M1-predominant polarization of Kupffer cells, and elevating the serum levels of inflammatory cytokines. In contrast, TGR5 activation inhibited ROS production, secretion of pro-inflammatory cytokines, and M1-predominant polarization of Kupffer cells. Moreover, results showed that TGR5 exerted its effects via suppressing NF-κB signaling and activating nuclear factor 2 (Nrf2)/HO-1 signaling. Finally, the effect of TGR5 on cholestatic liver damage was also confirmed in vivo.

conclusionsTGR5 activation protected against BDL-induced CLD by both suppressing inflammation via inhibiting the NF-κB pathway and reducing ROS production via activation of Nrf2/HO-1 signaling. These findings show the importance of TGR5 in CLD and provide new insight into therapeutic strategies for CLD.

Indexed as

Cholestatic liver disease (CLD)inflammationinflammatory cytokinesreactive oxygen speciesTGR5

Identifiers

PMID34430599
PMCPMC8350648
OpenAlexW3179129942

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.