Evidence map›Paper›PMID 41896470›Full record

ArticleCell biology and toxicology2026

Unveiling a novel macrophage-driven mechanism for obeticholic acid-induced liver injury in cholestatic: targeting NLRP12

Jie Wang, Zihang Yuan, Haoran Zhang, Qianhui Tang, Yingying Miao, Anqin Li, Qingyu Chen, Xiaoyan Zhou, Qinwei Yu, Luyong Zhang and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell biology and toxicology, 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
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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

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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

11 authors.

Jie WangNew Drug Screening and Pharmacodynamics Evaluation Center, Jiangsu Center for Pharmacodynamics Research and Evaluation, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China.
Zihang YuanNew Drug Screening and Pharmacodynamics Evaluation Center, Jiangsu Center for Pharmacodynamics Research and Evaluation, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China.
Haoran ZhangNew Drug Screening and Pharmacodynamics Evaluation Center, Jiangsu Center for Pharmacodynamics Research and Evaluation, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China.
Qianhui TangNew Drug Screening and Pharmacodynamics Evaluation Center, Jiangsu Center for Pharmacodynamics Research and Evaluation, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China.
Yingying MiaoNew Drug Screening and Pharmacodynamics Evaluation Center, Jiangsu Center for Pharmacodynamics Research and Evaluation, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China.
Anqin LiNew Drug Screening and Pharmacodynamics Evaluation Center, Jiangsu Center for Pharmacodynamics Research and Evaluation, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China.
Qingyu ChenNew Drug Screening and Pharmacodynamics Evaluation Center, Jiangsu Center for Pharmacodynamics Research and Evaluation, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China.
Xiaoyan ZhouNew Drug Screening and Pharmacodynamics Evaluation Center, Jiangsu Center for Pharmacodynamics Research and Evaluation, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China.
Qinwei YuNew Drug Screening and Pharmacodynamics Evaluation Center, Jiangsu Center for Pharmacodynamics Research and Evaluation, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China. 1520200015@cpu.edu.cn.
Luyong ZhangNew Drug Screening and Pharmacodynamics Evaluation Center, Jiangsu Center for Pharmacodynamics Research and Evaluation, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China. lyzhang@cpu.edu.cn.
Zhenzhou JiangNew Drug Screening and Pharmacodynamics Evaluation Center, Jiangsu Center for Pharmacodynamics Research and Evaluation, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China. beaglejiang@cpu.edu.cn.

Funding

"Double First-Class" University project CPU2018GY33National Natural Science Foundation of China 82274200Natural Science Foundation of Jiangsu Province BK20221526
6 · The paper itself

Abstract

For individuals with Primary Biliary Cholangitis (PBC) who are either intolerant or nonresponsive to ursodeoxycholic acid (UDCA), obeticholic acid (OCA) is authorized as a therapeutic treatment. Nevertheless, its clinical application has been limited due to the occurrence of several adverse effects. We employed the bile duct ligation (BDL) model to simulate cholestatic conditions observed in patients, revealing that high doses of OCA exacerbated hepatic inflammatory infiltration and fibrosis, accompanied by a marked augmentation in the extent of ductular reaction (DR) within BDL. Our findings mentioned that macrophages played a critical part in mediating OCA-induced aggravation of DR. OCA significantly upregulated the non-canonical NF-κB Relb signaling in macrophages, thereby contributing to proliferation of cholangiocytes. Cellular thermal shift assay (CETSA), surface plasma resonance (SPR) and liquid chromatography mass spectrometer (LC-MS) analysis showed that OCA directly bond to Nucleotide-binding oligomerization domain-like receptor (NLR) pyrin domain (PYD)-containing protein 12 (NLRP12), leading to a reduction in its protein level. Further, activity-based protein profiling (ABPP) method identified the Arg185 residue of NLRP12 as the binding site for OCA, elucidating the mechanism by which OCA downregulates NLRP12 protein expression. This interaction diminished the inhibitory effect of NLRP12 on the Relb pathway. Collectively, our study delineated the NLRP12

Indexed as

Chemical and Drug Induced Liver InjuryChenodeoxycholic AcidCholestasisMacrophagesTranscription Factor RelBAnimalsBile DuctsLiverMaleMiceMice, Inbred C57BLSignal TransductionChenodeoxycholic Acidobeticholic acidRelb protein, mouseTranscription Factor RelBCholestasisDuctular reactionMacrophageNLRP12Obeticholic acidRelb

Identifiers

PMID41896470
PMCPMC13149613

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.