Evidence map›Paper›PMID 32561593›Full record

ArticleDrug metabolism and disposition: the biological fate of chemicals2020

Dexamethasone-Induced Liver Enlargement Is Related to PXR/YAP Activation and Lipid Accumulation but Not Hepatocyte Proliferation.

Tingying Jiao, Xinpeng Yao, Yingyuan Zhao, Yanying Zhou, Yue Gao, Shicheng Fan, Panpan Chen, Xuan Li, Yiming Jiang, Xiao Yang and 3 more

Erratum issuedOpen access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Drug metabolism and disposition: the biological fate of chemicals, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
4.3field-weighted citation impact, top 5% 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

21 citing papers in PubMed, 43 citations in OpenAlex.

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  19. Review
  20. Disease-drug and drug-drug interaction in COVID-19: Risk and assessment.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2021
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 3 institutions in 2 countries.

Tingying JiaoGuangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China (T.J., X.P.Y., Yi.Z., Ya.Z., Y.G., S.F., P.C., X.L., Y.J., X.Y., M.H., H.B.) and Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland (F.J.G.).
Xinpeng YaoGuangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China (T.J., X.P.Y., Yi.Z., Ya.Z., Y.G., S.F., P.C., X.L., Y.J., X.Y., M.H., H.B.) and Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland (F.J.G.).
Yingyuan ZhaoGuangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China (T.J., X.P.Y., Yi.Z., Ya.Z., Y.G., S.F., P.C., X.L., Y.J., X.Y., M.H., H.B.) and Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland (F.J.G.).
Yanying ZhouGuangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China (T.J., X.P.Y., Yi.Z., Ya.Z., Y.G., S.F., P.C., X.L., Y.J., X.Y., M.H., H.B.) and Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland (F.J.G.) bihchang@mail.sysu.edu.cn.
Yue GaoGuangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China (T.J., X.P.Y., Yi.Z., Ya.Z., Y.G., S.F., P.C., X.L., Y.J., X.Y., M.H., H.B.) and Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland (F.J.G.).
Shicheng FanGuangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China (T.J., X.P.Y., Yi.Z., Ya.Z., Y.G., S.F., P.C., X.L., Y.J., X.Y., M.H., H.B.) and Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland (F.J.G.).
Panpan ChenGuangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China (T.J., X.P.Y., Yi.Z., Ya.Z., Y.G., S.F., P.C., X.L., Y.J., X.Y., M.H., H.B.) and Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland (F.J.G.).
Xuan LiGuangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China (T.J., X.P.Y., Yi.Z., Ya.Z., Y.G., S.F., P.C., X.L., Y.J., X.Y., M.H., H.B.) and Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland (F.J.G.).
Yiming JiangGuangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China (T.J., X.P.Y., Yi.Z., Ya.Z., Y.G., S.F., P.C., X.L., Y.J., X.Y., M.H., H.B.) and Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland (F.J.G.).
Xiao YangGuangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China (T.J., X.P.Y., Yi.Z., Ya.Z., Y.G., S.F., P.C., X.L., Y.J., X.Y., M.H., H.B.) and Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland (F.J.G.).
Frank J GonzalezGuangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China (T.J., X.P.Y., Yi.Z., Ya.Z., Y.G., S.F., P.C., X.L., Y.J., X.Y., M.H., H.B.) and Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland (F.J.G.).
Min HuangGuangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China (T.J., X.P.Y., Yi.Z., Ya.Z., Y.G., S.F., P.C., X.L., Y.J., X.Y., M.H., H.B.) and Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland (F.J.G.).
Huichang BiGuangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China (T.J., X.P.Y., Yi.Z., Ya.Z., Y.G., S.F., P.C., X.L., Y.J., X.Y., M.H., H.B.) and Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland (F.J.G.) bihchang@mail.sysu.edu.cn.
National Cancer Institute · USCenter for Cancer Research · USSun Yat-sen University · CN

Funding

Xenobiotic receptorsZIABC005562 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI GONZALEZ, FRANK J · 2009 to 2025
$26.9M
6 · The paper itself

Abstract

Dexamethasone (Dex), a widely prescribed anti-inflammatory drug, was reported to induce liver enlargement (hepatomegaly) in clinical practice and in animal models. However, the underlying mechanisms are not elucidated. Dex is a known activator of pregnane X receptor (PXR). Yes-associated protein (YAP) has been implicated in chemically induced liver enlargement. Here, the roles of PXR and YAP pathways were investigated in Dex-induced hepatomegaly. Upregulation of PXR downstream proteins, including cytochrome P450 (CYP) 3A11, 2B10, and organic anion transporter polypeptide 2 (OATP2), indicated PXR signaling was activated after high dose of Dex (50 mg/kg, i.p.), and Dex at 100 μM activated PXR in the dual-luciferase reporter gene assay. Dex also increased the expression of total YAP, nuclear YAP, and YAP downstream proteins, including connective tissue growth factor and cysteine-rich angiogenic inducer 61, indicating activation of the YAP pathway. Furthermore, nuclear translocation of YAP was promoted by activation of PXR. However, hepatocyte proliferation was inhibited with significant decrease in the expression of proliferation-related proteins cyclin D1 and proliferating cell nuclear antigen as well as other regulatory factors, such as forkhead box protein M1, c-MYC, and epidermal growth factor receptor. The inhibitory effect of Dex on hepatocyte proliferation was likely due to its anti-inflammation effect of suppression of inflammation factors. β-catenin staining revealed enlarged hepatocytes, which were mostly attributable to the accumulation of lipids, such as triglycerides. In summary, high-dose Dex increased liver size accompanied by enlarged hepatocytes, and this was due to the activation of PXR/YAP and their effects on lipid accumulation but not hepatocyte proliferation. These findings provide new insights for understanding the mechanism of Dex-induced hepatomegaly. SIGNIFICANCE STATEMENT: This study identified the roles of pregnane X receptor (PXR) and yes-associated protein (YAP) pathways in dexamethasone (Dex)-induced hepatomegaly. Dex induced PXR/YAP activation, enlarged hepatocytes, and promoted liver enlargement with lipid accumulation, such as triglycerides. However, hepatocyte proliferation was inhibited by the anti-inflammatory effect of Dex. These findings provide new insights for understanding the mechanism of Dex-induced hepatomegaly.

Indexed as

Adaptor Proteins, Signal TransducingAnimalsCell ProliferationDexamethasoneDisease Models, AnimalHEK293 CellsHepatocytesHepatomegalyHep G2 CellsHumansLipid MetabolismLiverMaleMicePregnane X ReceptorSincalideAdaptor Proteins, Signal TransducingDexamethasoneNR1I2 protein, humanNr1i2 protein, mousePregnane X ReceptorSincalideTranscription FactorsTriglyceridesYAP1 protein, humanYap1 protein, mouseYAP-Signaling Proteins

Identifiers

PMID32561593
PMCPMC7497622
OpenAlexW3036645012

What OpenQuestion holds

Textmetadata
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 OpenQuestion graph.