Evidence mapPaperPMID 42536664Full record

ArticlePLoS neglected tropical diseases2026

Hexokinase-3 upregulation and histone H3K18 lactylation mediate murine liver fibrosis induced by Echinococcus multilocularis.

Yurun Miao, Lixian Shan, Jing Liu, Wei Cui, Xiangyang Yang, Lei Xiu, Wenbin Yang, Chunfu Li, Wenhui Liu, Yan Wang and 2 more

Abstract read
In one paragraph

Article in PLoS neglected tropical diseases, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

12 authors.

Yurun MiaoThe State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, School of Life Sciences, Inner Mongolia University, Hohhot, China.
Lixian ShanThe State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, School of Life Sciences, Inner Mongolia University, Hohhot, China.
Jing LiuThe State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, School of Life Sciences, Inner Mongolia University, Hohhot, China.
Wei CuiThe State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, School of Life Sciences, Inner Mongolia University, Hohhot, China.
Xiangyang YangThe State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, School of Life Sciences, Inner Mongolia University, Hohhot, China.
Lei XiuThe State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, School of Life Sciences, Inner Mongolia University, Hohhot, China.
Wenbin YangThe State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, School of Life Sciences, Inner Mongolia University, Hohhot, China.
Chunfu LiThe State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, School of Life Sciences, Inner Mongolia University, Hohhot, China.
Wenhui LiuDepartment of Medicine, College of Hetao, Bayannur, China.
Yan WangDepartment of Medicine, College of Hetao, Bayannur, China.
Ting ZhangThe State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, School of Life Sciences, Inner Mongolia University, Hohhot, China.ORCID https://orcid.org/0000-0001-7383-5090
Wei HuThe State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, School of Life Sciences, Inner Mongolia University, Hohhot, China.ORCID https://orcid.org/0000-0001-6070-5529

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Alveolar echinococcosis (AE), caused by Echinococcus multilocularis infection, leads to destructive hepatic lesions and severe hepatic fibrosis. Lactylation, a post-translational modification, has been linked to fibrotic progression in hepatocytes. However, the role of E. multilocularis infection in hepatic lactylation remains unclear. This study aims to elucidate the relationship between hepatic fibrosis and lactylation induced by E. multilocularis infection and fill this knowledge gap. The results showed that lactate concentrations in the livers and sera of AE mice were significantly elevated compared with those in the control group. The relative mRNA expression of hexokinase isoforms in the liver tissue of AE mouse models revealed significant upregulation of hexokinase-3 (HK3), a key enzyme regulating lactate production. Immunofluorescence staining revealed substantial colocalization between HK3 and TGF-β1 in hepatic lesions of AE mice. Western blot analysis using a pan-lactylation antibody showed significantly elevated lactylation levels in the livers of AE mice compared with controls, with a significant increase in histone H3 lysine 18 lactylation (H3K18la). CUT&Tag analysis revealed differential enrichment of H3K18la at multiple fibrosis-associated genes in AE mouse liver. In vitro, AML-12 hepatocytes exposed to E. multilocularis culture supernatant showed significant upregulation of TGF-β1, HK3, and histone lactylation. HK3 knockdown significantly reduced the induction of H3K18la and fibrosis-related proteins, whereas exogenous lactate supplementation significantly increased these responses despite HK3 silencing, confirming that lactate acts downstream of HK3 to drive histone lactylation and fibrogenesis. Corosolic acid, a compound that limits HK3-mediated lactate production, attenuated histone lactylation and fibrosis-related protein expression. These findings indicate that HK3-driven histone lactylation at H3K18 contributes to hepatic fibrosis in AE, and suggest that HK3 may serve as promising therapeutic targets for AE.

Indexed as

EchinococcosisEchinococcosis, HepaticEchinococcus multilocularisHexokinaseHistonesLiver CirrhosisAnimalsDisease Models, AnimalFemaleHepatocytesLactic AcidLiverMaleMiceProtein Processing, Post-TranslationalTransforming Growth Factor beta1HexokinaseHistonesLactic AcidTransforming Growth Factor beta1

Identifiers

PMID42536664
PMCPMC13460742

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.