The m6A Reader IGF2BP2 Regulates Macrophage Phenotypic Activation and Inflammatory Diseases by Stabilizing TSC1 and PPARγ.

Wang, Xia; Ji, Yuge; Feng, Panpan; Liu, Rucheng; Li, Guosheng; Zheng, Junjie; Xue, Yaqiang; Wei, Yaxun; Ji, Chunyan; Chen, Dawei; Li, Jingxin

doi:10.1002/advs.202100209

Article (Scientific journals)

The m6A Reader IGF2BP2 Regulates Macrophage Phenotypic Activation and Inflammatory Diseases by Stabilizing TSC1 and PPARγ.

Wang, Xia; Ji, Yuge; Feng, Panpan et al.

2021 • In Advanced Science, 8 (13), p. 2100209

Peer reviewed

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https://hdl.handle.net/2268/290538

DOI
10.1002/advs.202100209

PubMed
34258163

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Keywords :

IGF2BP2; TSC1; inflammatory diseases; m6A reader; macrophage polarization; IGF2BP2 protein, mouse; PPAR gamma; RNA-Binding Proteins; Tsc1 protein, mouse; Tuberous Sclerosis Complex 1 Protein; Animals; Cell Differentiation/genetics; Disease Models, Animal; Female; Inflammation/genetics; Inflammation/metabolism; Macrophage Activation/genetics; Male; Mice; Mice, Inbred C57BL; PPAR gamma/genetics; PPAR gamma/metabolism; Phenotype; RNA-Binding Proteins/genetics; RNA-Binding Proteins/metabolism; Signal Transduction/genetics; Tuberous Sclerosis Complex 1 Protein/genetics; Tuberous Sclerosis Complex 1 Protein/metabolism; Allergic inflammation; Dextran sulfate sodium; High-mobility groups; Inflammatory disease; Insulin-like growth factor 2; Messenger RNAs (mRNA); Therapeutic targets; Tuberous sclerosis; Cell Differentiation; Inflammation; Macrophage Activation; Signal Transduction; Medicine (miscellaneous); Chemical Engineering (all); Materials Science (all); Biochemistry, Genetics and Molecular Biology (miscellaneous); Engineering (all); Physics and Astronomy (all); General Physics and Astronomy; General Engineering; General Materials Science; General Chemical Engineering

Abstract :

[en] Phenotypic polarization of macrophages is regulated by a milieu of cues in the local tissue microenvironment. Currently, little is known about how the intrinsic regulators modulate proinflammatory (M1) versus prohealing (M2) macrophages activation. Here, it is observed that insulin-like growth factor 2 messenger RNA (mRNA)-binding protein 2 (IGF2BP2)-deleted macrophages exhibit enhanced M1 phenotype and promote dextran sulfate sodium induced colitis development. However, the IGF2BP2-/- macrophages are refractory to interleukin-4 (IL-4) induced activation and alleviate cockroach extract induced pulmonary allergic inflammation. Molecular studies indicate that IGF2BP2 switches M1 macrophages to M2 activation by targeting tuberous sclerosis 1 via an N6-methyladenosine (m6A)-dependent manner. Additionally, it is also shown a signal transducer and activators of transcription 6 (STAT6)-high mobility group AT-hook 2-IGF2BP2-peroxisome proliferator activated receptor-γ axis involves in M2 macrophages differentiation. These findings highlight a key role of IGF2BP2 in regulation of macrophages activation and imply a potential therapeutic target of macrophages in the inflammatory diseases.

Disciplines :

Immunology & infectious disease

Author, co-author :

Wang, Xia; Department of Physiology School of Basic Medical Sciences Cheeloo College of Medicine Shandong University Jinan Shandong 250012 China

Ji, Yuge; Department of Physiology School of Basic Medical Sciences Cheeloo College of Medicine Shandong University Jinan Shandong 250012 China

Feng, Panpan; Department of Hematology Qilu Hospital Cheeloo College of Medicine Shandong University Jinan Shandong 250012 China

Liu, Rucheng; Department of Physiology School of Basic Medical Sciences Cheeloo College of Medicine Shandong University Jinan Shandong 250012 China

Li, Guosheng; Department of Hematology Qilu Hospital Cheeloo College of Medicine Shandong University Jinan Shandong 250012 China

Zheng, Junjie; Department of Physiology School of Basic Medical Sciences Cheeloo College of Medicine Shandong University Jinan Shandong 250012 China

Xue, Yaqiang; ABLife BioBigData Institute Wuhan Hubei 430075 China

Wei, Yaxun; Center for Genoem Analysis ABLife Inc. Wuhan Hubei 430075 China

Ji, Chunyan; Department of Hematology Qilu Hospital Cheeloo College of Medicine Shandong University Jinan Shandong 250012 China

Chen, Dawei ; Université de Liège - ULiège > GIGA

Li, Jingxin; Department of Physiology School of Basic Medical Sciences Cheeloo College of Medicine Shandong University Jinan Shandong 250012 China

Language :

English

Title :

The m6A Reader IGF2BP2 Regulates Macrophage Phenotypic Activation and Inflammatory Diseases by Stabilizing TSC1 and PPARγ.

Publication date :

2021

Journal title :

Advanced Science

ISSN :

2198-3844

Publisher :

John Wiley and Sons Inc, Germany

Volume :

Issue :

Pages :

2100209

Peer reviewed :

Peer reviewed

Additional URL :

https://onlinelibrary.wiley.com/doi/pdf/10.1002/advs.202100209

Funders :

NSCF - National Natural Science Foundation of China

Funding text :

The authors thank Dr. Liu Hong-bin of Shandong University for providing the IGF2BP2?/? mice and C. Zhang for technical assistance. Special thanks go to Prof. Zhen Junhui from Pathology Department of Qilu Hospital for providing ulcerative colitis (UC) samples. This work was supported by grants from the National Natural Science Foundation of China (31971061), National Key Research and Development Program of China (2016YFC1302203), and Taishan Scholars Program.The authors thank Dr. Liu Hong‐bin of Shandong University for providing the IGF2BP2 mice and C. Zhang for technical assistance. Special thanks go to Prof. Zhen Junhui from Pathology Department of Qilu Hospital for providing ulcerative colitis (UC) samples. This work was supported by grants from the National Natural Science Foundation of China (31971061), National Key Research and Development Program of China (2016YFC1302203), and Taishan Scholars Program. −/−

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