Evidence map›Paper›PMID 41842990›Full record

ArticleThe Journal of clinical investigation2026

Epigenetically controlled endothelial promyelocytic leukemia drives liver inflammation and fibrosis.

Can Gan, Enjiang Lai, Yang Tai, Shuai Chen, Chong Zhao, Wenting Dai, Zhu Yang, Bei Li, Tian Lan, Yang Xiao and 13 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of clinical investigation, 2026. 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
–field-weighted citation impact
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.

  1. Review
  2. Article
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

23 authors.

Can GanDepartment of Gastroenterology, Lab of Gastroenterology and Hepatology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
Enjiang LaiDepartment of Gastroenterology, Lab of Gastroenterology and Hepatology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
Yang TaiDepartment of Gastroenterology, Lab of Gastroenterology and Hepatology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
Shuai ChenDepartment of Gastroenterology and Hepatology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China.
Chong ZhaoDepartment of Gastroenterology, Lab of Gastroenterology and Hepatology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
Wenting DaiDepartment of Gastroenterology, Lab of Gastroenterology and Hepatology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
Zhu YangDepartment of Gastroenterology, Lab of Gastroenterology and Hepatology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
Bei LiDepartment of Biliary Surgery, West China Hospital, Sichuan University, Chengdu, China.
Tian LanDepartment of Gastroenterology, Lab of Gastroenterology and Hepatology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
Yang XiaoDepartment of Gastroenterology, Lab of Gastroenterology and Hepatology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
Yangkun GuoDepartment of Gastroenterology, Lab of Gastroenterology and Hepatology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
Jiaxin ChenDepartment of Gastroenterology, Lab of Gastroenterology and Hepatology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
Bo WeiDepartment of Gastroenterology, Lab of Gastroenterology and Hepatology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
Zhaodi CheThe First Affiliated Hospital, Key Laboratory of Regenerative Medicine of Ministry of Education, College of Life Science and Technology, Jinan University, Guangzhou, Guangdong, China.
Sheng CaoDivision of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA.
Mengfei LiuDivision of Digestive Disease, Internal Medicine, Yale University, New Haven, Connecticut, USA.
Frank TackeDepartment of Hepatology and Gastroenterology, Campus Virchow-Klinikum and Campus Charité Mitte, Charité - Universitätsmedizin Berlin, Berlin, Germany.
Chengwei TangDepartment of Gastroenterology, Lab of Gastroenterology and Hepatology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
Vijay H ShahDivision of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA.
Haopeng YuWest China Biomedical Big Data Center, West China Hospital/West China School of Medicine, Sichuan University, Chengdu, China.
Fei WangThe First Affiliated Hospital, Key Laboratory of Regenerative Medicine of Ministry of Education, College of Life Science and Technology, Jinan University, Guangzhou, Guangdong, China.
Zhiyin HuangDepartment of Gastroenterology, Lab of Gastroenterology and Hepatology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
Jinhang GaoDepartment of Gastroenterology, Lab of Gastroenterology and Hepatology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.

Funding

IL17 dependent angiocrine signaling drives inflammation in alcohol associated hepatitisK08AA030587 · NIAAA · YALE UNIVERSITY · PI Mengfei Liu · 2022 to 2026
$1.0M
NIAAA NIH HHS K08 AA030587
6 · The paper itself

Abstract

Cellular and molecular heterogeneity in the liver has been increasingly recognized to drive liver fibrosis progression, but the particular events that occur initially in response to liver injury and trigger immune cell recruitment remain unclear. Here, we identify epigenetically aberrant liver sinusoidal endothelial cells (LSECs) as key players in this process. Mechanistically, the epigenetic readers like bromodomain-containing protein 4-dependent (BRD4-dependent) super enhancers (SEs) activate proinflammatory genes, including promyelocytic leukemia (PML). The PML protein, in turn, binds BRD4 and amplifies proinflammatory angiocrine signaling through phase separation-dependent SE activation via PML/BRD4 condensate formation. In mouse models, LSEC-specific depletion of the PML/BRD4 complex mitigates liver inflammation and fibrosis. Single-cell RNA-seq reveals that epigenetically aberrant LSECs exhibit a reprogrammed proinflammatory angiocrine landscape in mouse fibrotic livers. TIMP1+ LSECs promote the recruitment of CD63+ monocyte-derived macrophages (MoMFs) during liver fibrosis progression. Thereby, PML/BRD4 in LSECs governs inflammatory immune cell recruitment in liver fibrosis. Pharmacological BRD4 inhibition or epigenetic PML-SE repression alleviates liver inflammation and fibrosis. In conclusion, PML/BRD4-mediated SE activation via phase separation drives proinflammatory angiocrine signaling in LSECs, initiating the inflammatory cascade and subsequent immune cell recruitment during liver fibrosis.

Indexed as

Endothelial CellsEpigenesis, GeneticHepatitisLiver CirrhosisPromyelocytic Leukemia ProteinTranscription FactorsAnimalsBromodomain Containing ProteinsCell Cycle ProteinsHumansMiceNuclear ProteinsSuper EnhancersBRD4 protein, humanBrd4 protein, mouseBromodomain Containing ProteinsCell Cycle ProteinsNuclear ProteinsPML protein, humanPml protein, mousePromyelocytic Leukemia ProteinTranscription FactorsEndothelial cellsEpigeneticsFibrosisGastroenterologyHepatology

Identifiers

PMID41842990
PMCPMC13221223

What Socratic 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 Socratic graph.