Osteopontin Promotes Macrophage M1 Polarization by Activation of the JAK1/STAT1/HMGB1 Signaling Pathway in Nonalcoholic Fatty Liver Disease

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Abstract

Background and Aims

Osteopontin (OPN) is reported to be associated with the pathogenesis of nonalcoholic fatty liver disease (NAFLD). However, the function of OPN in NAFLD is still inconclusive. Therefore, our aim in this study was to evaluate the role of OPN in NAFLD and clarify the involved mechanisms.

Methods

We analyzed the expression change of OPN in NAFLD by bioinformatic analysis, qRT-PCR, western blotting and immunofluorescence staining. To clarify the role of OPN in NAFLD, the effect of OPN from HepG2 cells on macrophage polarization and the involved mechanisms were examined by FACS and western blotting.

Results

OPN was significantly upregulated in NAFLD patients compared with normal volunteers by microarray data, and the high expression of OPN was related with disease stage and progression. OPN level was also significantly increased in liver tissue samples of NAFLD from human and mouse, and in HepG2 cells treated with oleic acid (OA). Furthermore, the supernatants of OPN-treated HepG2 cells promoted the macrophage M1 polarization. Mechanistically, OPN activated the janus kinase 1(JAK1)/signal transducers and activators of transcription 1 (STAT1) signaling pathway in HepG2 cells, and consequently HepG2 cells secreted more high-mobility group box 1 (HMGB1), thereby promoting macrophage M1 polarization.

Conclusions

OPN promoted macrophage M1 polarization by increasing JAK1/STAT1-induced HMGB1 secretion in hepatocytes.

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Most cited references 40

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Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group.

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Because of the pressure for timely, informed decisions in public health and clinical practice and the explosion of information in the scientific literature, research results must be synthesized. Meta-analyses are increasingly used to address this problem, and they often evaluate observational studies. A workshop was held in Atlanta, Ga, in April 1997, to examine the reporting of meta-analyses of observational studies and to make recommendations to aid authors, reviewers, editors, and readers. Twenty-seven participants were selected by a steering committee, based on expertise in clinical practice, trials, statistics, epidemiology, social sciences, and biomedical editing. Deliberations of the workshop were open to other interested scientists. Funding for this activity was provided by the Centers for Disease Control and Prevention. We conducted a systematic review of the published literature on the conduct and reporting of meta-analyses in observational studies using MEDLINE, Educational Research Information Center (ERIC), PsycLIT, and the Current Index to Statistics. We also examined reference lists of the 32 studies retrieved and contacted experts in the field. Participants were assigned to small-group discussions on the subjects of bias, searching and abstracting, heterogeneity, study categorization, and statistical methods. From the material presented at the workshop, the authors developed a checklist summarizing recommendations for reporting meta-analyses of observational studies. The checklist and supporting evidence were circulated to all conference attendees and additional experts. All suggestions for revisions were addressed. The proposed checklist contains specifications for reporting of meta-analyses of observational studies in epidemiology, including background, search strategy, methods, results, discussion, and conclusion. Use of the checklist should improve the usefulness of meta-analyses for authors, reviewers, editors, readers, and decision makers. An evaluation plan is suggested and research areas are explored.

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Mechanisms of NAFLD development and therapeutic strategies

Mary Rinella, Arun Sanyal, Scott Friedman … (2018)

There has been a rise in the prevalence of nonalcoholic fatty liver disease (NAFLD), paralleling a worldwide increase in diabetes and metabolic syndrome. NAFLD, a continuum of liver abnormalities from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH), has a variable course but can lead to cirrhosis and liver cancer. Here we review the pathogenic and clinical features of NAFLD, its major comorbidities, clinical progression and risk of complications and in vitro and animal models of NAFLD enabling refinement of therapeutic targets that can accelerate drug development. We also discuss evolving principles of clinical trial design to evaluate drug efficacy and the emerging targets for drug development that involve either single agents or combination therapies intended to arrest or reverse disease progression.

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Is Open Access

Pathview: an R/Bioconductor package for pathway-based data integration and visualization

Weijun Luo, Cory Brouwer (2013)

Summary: Pathview is a novel tool set for pathway-based data integration and visualization. It maps and renders user data on relevant pathway graphs. Users only need to supply their data and specify the target pathway. Pathview automatically downloads the pathway graph data, parses the data file, maps and integrates user data onto the pathway and renders pathway graphs with the mapped data. Although built as a stand-alone program, Pathview may seamlessly integrate with pathway and functional analysis tools for large-scale and fully automated analysis pipelines. Availability: The package is freely available under the GPLv3 license through Bioconductor and R-Forge. It is available at http://bioconductor.org/packages/release/bioc/html/pathview.html and at http://Pathview.r-forge.r-project.org/. Contact: luo_weijun@yahoo.com Supplementary information: Supplementary data are available at Bioinformatics online.

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Author and article information

Journal

Journal ID (nlm-ta): J Clin Transl Hepatol

Journal ID (iso-abbrev): J Clin Transl Hepatol

Journal ID (publisher-id): JCTH

Title: Journal of Clinical and Translational Hepatology

Publisher: XIA & HE Publishing Inc.

ISSN (Print): 2225-0719

ISSN (Electronic): 2310-8819

Publication date (Print): 28 April 2023

Publication date (Electronic): 31 May 2022

Volume: 11

Issue: 2

Pages: 273-283

Affiliations

[1 ]The Institute of Translational Medicine, Nanchang University, Nanchang, Jiangxi, China

[2 ]School of Pharmacy, Nanchang University, Nanchang, Jiangxi, China

[3 ]Central Laboratory, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, Zhejiang, China

[4 ]Jiangxi Provincial Key Laboratory of Preventive Medicine, School of Public Health, Nanchang University, Nanchang, Jiangxi, China

[5 ]School of Basic Medical Science, Nanchang University, Nanchang, Jiangxi, China

Author notes

[* ] Correspondence to: Meixiu Jiang, The Institute of Translational Medicine, Nanchang University, 999 Xuefu Road, Nanchang, Jiangxi 330031, China. ORCID: https://orcid.org/0000-0001-8747-6877. Tel: +86-15979167569, Fax: +86-791-83827165, E-mail: jiangmxs@ 123456163.com ; Libin Deng, Jiangxi Provincial Key Laboratory of Preventive Medicine, School of Public Health, Nanchang University, 999 Xuefu Road, Nanchang, Jiangxi 330031, China. ORCID: https://orcid.org/0000-0001-5863-3829. Tel: +86-15170401580, Fax: +86-791-83827165, E-mail: denglb1937@ 123456163.com

[#]

Contributed equally to this work.

This study was supported by National Natural Science Foundation of China grants (81760089, 82160094 to MJ; 82060112 to LD) and Jiangxi Provincial Department of Science and Technology, China (20202BAB206087 to MJ).

The authors have no conflict of interests related to this publication.

Study concept and design (MJ, LD), acquisition of data (ZX, FX, XD, YN, DW, CP, XZ), analysis and interpretation of data (WL, NS, CC, ZZ, MJ), drafting of the manuscript (FX), critical revision of the manuscript for important intellectual content (MJ, LD), administrative, technical, or material support, study supervision (MJ, LD).

Author information

Libin Deng https://orcid.org/0000-0001-5863-3829

Meixiu Jiang https://orcid.org/0000-0001-8747-6877

Article

Publisher ID: JCTH.2021.00474

DOI: 10.14218/JCTH.2021.00474

PMC ID: 9817049

PubMed ID: 36643029

SO-VID: bbbce072-15d6-43f8-918d-484b8449fac6

License:

This is an Open Access article distributed under the terms of the Creative Commons Attribution-Noncommercial 4.0 International License (CC BY-NC 4.0), permitting all non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

History

Date received : 23 October 2021

Date revision received : 12 April 2022

Date accepted : 5 May 2022

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Osteopontin Promotes Macrophage M1 Polarization by Activation of the JAK1/STAT1/HMGB1 Signaling Pathway in Nonalcoholic Fatty Liver Disease

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Abstract

Background and Aims

Methods

Results

Conclusions

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Most cited references 40

Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group.

Mechanisms of NAFLD development and therapeutic strategies

Pathview: an R/Bioconductor package for pathway-based data integration and visualization

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