Evidence map›Paper›PMID 41708585›Full record

ArticleSignal transduction and targeted therapy2026

Serpina3c protects against metabolic dysfunction-associated steatotic liver disease in offspring induced by prenatal prednisone exposure.

Yongguo Dai, Zhengjie Lu, Yu Peng, Kexin Liu, Xiaoqian Lu, Xiaoxiang Sun, Yuxi Wang, Xuerong Yan, Zijie Chen, Ziyi Zhang and 7 more

Abstract read
In one paragraph

Article in Signal transduction and targeted therapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
  2. Article
  3. 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

17 authors.

Yongguo Dai *Department of Pharmacology, Wuhan University School of Basic Medical Sciences, Wuhan, Hubei Province, China.ORCID http://orcid.org/0000-0002-9023-5211
Zhengjie Lu *Department of Pharmacology, Wuhan University School of Basic Medical Sciences, Wuhan, Hubei Province, China.
Yu PengDepartment of Pharmacology, Wuhan University School of Basic Medical Sciences, Wuhan, Hubei Province, China.
Kexin LiuDepartment of Pharmacology, Wuhan University School of Basic Medical Sciences, Wuhan, Hubei Province, China.
Xiaoqian LuDepartment of Pharmacology, Wuhan University School of Basic Medical Sciences, Wuhan, Hubei Province, China.
Xiaoxiang SunDepartment of Pharmacology, Wuhan University School of Basic Medical Sciences, Wuhan, Hubei Province, China.
Yuxi WangDepartment of Pharmacology, Wuhan University School of Basic Medical Sciences, Wuhan, Hubei Province, China.
Xuerong YanDepartment of Pharmacology, Wuhan University School of Basic Medical Sciences, Wuhan, Hubei Province, China.
Zijie ChenDepartment of Pharmacology, Wuhan University School of Basic Medical Sciences, Wuhan, Hubei Province, China.
Ziyi ZhangDepartment of Pharmacology, Wuhan University School of Basic Medical Sciences, Wuhan, Hubei Province, China.
Ning ZhangDepartment of Pharmacology, Wuhan University School of Basic Medical Sciences, Wuhan, Hubei Province, China.
Aihemaitijiang AilikaitiDepartment of Pharmacology, Wuhan University School of Basic Medical Sciences, Wuhan, Hubei Province, China.
Yiming ChenDepartment of Pharmacology, Wuhan University School of Basic Medical Sciences, Wuhan, Hubei Province, China.
Quanrui YueDepartment of Pharmacology, Wuhan University School of Basic Medical Sciences, Wuhan, Hubei Province, China.
Yu GuoDepartment of Pharmacology, Wuhan University School of Basic Medical Sciences, Wuhan, Hubei Province, China.
Liaobin ChenDepartment of Orthopedic Surgery, Joint Disease Research Center of Wuhan University, Zhongnan Hospital of Wuhan University, Wuhan, Hubei Province, China.ORCID http://orcid.org/0000-0002-8778-1457
Hui WangDepartment of Pharmacology, Wuhan University School of Basic Medical Sciences, Wuhan, Hubei Province, China. wanghui19@whu.edu.cn.ORCID http://orcid.org/0000-0001-5300-8661

Funding

National Natural Science Foundation of China (National Science Foundation of China) 82030111
6 · The paper itself

Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) has become a major global public health problem, and its occurrence is associated with adverse environmental exposures during development. In this study, we investigated the impact of the use of prednisone (a synthetic glucocorticoid drug) during pregnancy on susceptibility to MASLD in offspring and explored its potential therapeutic targets. Pregnant rodents were administered clinically equivalent doses of prednisone daily by oral gavage during gestation days (GDs) 0-20 in rats and GD0-18 mice, and their offspring were fed a high-fat diet from postnatal weeks 8-12. The results showed that prenatal prednisone exposure (PPE) led to reduced hepatic glucose uptake and fatty acid oxidation in offspring rats prenatally and postnatally and that the offspring developed more severe MASLD when fed a high-fat diet, with males exhibiting greater severity than females. Consistent findings were observed in PPE adult offspring mice. RNA-seq and experimental results revealed that hepatic Serpina3c expression was consistently reduced in PPE offspring before and after birth, which led to an increase in chymase-Ang II production and subsequent activation of its receptor AT1R, leading to MASLD susceptibility. In vivo and in vitro studies revealed that the programming of low Serpina3c expression was associated with reduced H3K27ac levels in the gene promoter region of Serpina3c caused by the activation of GR-HDAC3 signaling by the active metabolite prednisolone. Finally, postnatal high expression of hepatic Serpina3c reversed the activation of the chymase-Ang II-AT1R pathway and significantly ameliorated hepatic glucose and lipid metabolic dysfunction and MASLD susceptibility in PPE offspring. In summary, this study reveals MASLD susceptibility in offspring induced by PPE and identifies Serpina3c as a target for the prevention and treatment of MASLD susceptibility.

Indexed as

Fatty LiverMetabolic DiseasesPrednisonePrenatal Exposure Delayed EffectsSerpinsAnimalsDevelopmental Origins of Health and DiseaseDiet, High-FatFemaleHumansLiverMaleMicePregnancyRatsPrednisoneSERPINA3 protein, humanSerpins

Identifiers

PMID41708585
PMCPMC12917113

What Socratic 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 Socratic graph.