前列腺素E2促进c⁃Maf表达调控巨噬细胞骨架重构和吞噬能力的作用机制

孙素娟; 张雯雯; 曹艺格; 杜玄霜; 王茜铖; 徐睿萱; 罗凤玲; 刘敏

doi:10.14188/j.1671-8852.2024.0872

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前列腺素E2促进c⁃Maf表达调控巨噬细胞骨架重构和吞噬能力的作用机制

训练免疫专题研究 | 更新时间：2026-11-05

- 前列腺素E2促进c⁃Maf表达调控巨噬细胞骨架重构和吞噬能力的作用机制
  增强出版
- Mechanisms of prostaglandin E2⁃induced c⁃Maf expression in mediating macrophage cytoskeletal remodeling and phagocytic capacity
- 武汉大学学报（医学版） 2025年46卷第5期页码：575-582
- 作者机构：
  
  武汉大学泰康医学院（基础医学院）免疫学系湖北武汉 430071
- 作者简介：
  
  孙素娟，女，1997—，医学硕士生，主要从事肿瘤免疫及治疗的研究，E⁃mail：sunsujuan@whu.edu.cn
  刘敏，女，1977—，副教授，主要从事肿瘤免疫及治疗的研究，E⁃mail：mliu@whu.edu.cn
- 基金信息：
  
  国家自然科学基金资助项目(82272978;81971904)
- DOI：10.14188/j.1671-8852.2024.0872
  中图分类号： R378.911
- 收稿：2024-11-12，
  
  纸质出版：2025-05-25
- 稿件说明：
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孙素娟,张雯雯,曹艺格等.前列腺素E2促进c⁃Maf表达调控巨噬细胞骨架重构和吞噬能力的作用机制[J].武汉大学学报（医学版）,2025,46(05):575-582.

SUN Sujuan,ZHANG Wenwen,CAO Yige,et al.Mechanisms of prostaglandin E2⁃induced c⁃Maf expression in mediating macrophage cytoskeletal remodeling and phagocytic capacity[J].Medical Journal of Wuhan University,2025,46(05):575-582.
孙素娟,张雯雯,曹艺格等.前列腺素E2促进c⁃Maf表达调控巨噬细胞骨架重构和吞噬能力的作用机制[J].武汉大学学报（医学版）,2025,46(05):575-582. DOI： 10.14188/j.1671-8852.2024.0872.

SUN Sujuan,ZHANG Wenwen,CAO Yige,et al.Mechanisms of prostaglandin E2⁃induced c⁃Maf expression in mediating macrophage cytoskeletal remodeling and phagocytic capacity[J].Medical Journal of Wuhan University,2025,46(05):575-582. DOI： 10.14188/j.1671-8852.2024.0872.

摘要

目的

探究前列腺素E2（PGE2）对巨噬细胞c⁃Maf表达的调控作用机制及效应。

方法

本研究首先通过mRNA芯片测序和蛋白质谱分析，探讨c⁃Maf敲除对M2型巨噬细胞的基因及蛋白表达谱的影响，明确其在GO和KEGG通路中的调控作用。随后在RAW264.7巨噬细胞中进行c⁃Maf过表达(OE)和敲低(KD)实验，采用RT⁃qPCR、Western Blot、流式细胞术及免疫荧光染色等方法，评估不同c⁃Maf表达水平下巨噬细胞的形态、吞噬能力及骨架蛋白分布变化。同时，检测PGE2对RAW264.7细胞c⁃Maf的表达及其下游PI3K/AKT信号通路的调控，并通过PI3K抑制剂进一步分析该通路在PGE2诱导c⁃Maf表达中的作用。

结果

mRNA芯片和蛋白质谱结果表明，c⁃Maf敲除显著影响了巨噬细胞的多条关键通路，尤其是细胞膜及与吞噬作用和细胞骨架重构等相关通路。此外，PGE2通过PI3K/AKT信号通路上调c⁃Maf的表达，降低了巨噬细胞的吞噬能力并促进了骨架蛋白F⁃actin的重构。PI3K抑制剂显著抑制了PGE2对c⁃Maf的上调作用，提示PI3K/AKT通路在这一过程中起到关键调控作用。

结论

本研究表明，PGE2通过上调c⁃Maf表达，介导巨噬细胞吞噬能力的降低和骨架重构，而这一过程依赖于PI3K/AKT信号通路的激活。c⁃Maf在调控巨噬细胞功能中的核心作用为免疫系统调控和肿瘤免疫治疗提供了新的靶点。

Abstract

Objective

To investigate the role and the effect of prostaglandin E2 (PGE2) in regulating c⁃Maf expression in macrophages.

Methods

We first performed mRNA microarray and proteomics analyses to examine the impact of c⁃Maf knockout on gene and protein expression profiles in M2 macrophages

focusing on the associated GO and KEGG pathways. Subsequently

in RAW264.7 macrophages with c⁃Maf overexpression (OE) or knockdown (KD)

we utilized RT⁃qPCR

Western Blot

hematoxylin staining

flow cytometry

and F⁃actin staining to assess morphological changes

phagocytic capacity

and cytoskeletal protein distribution under different c⁃Maf expression levels. Additionally

we examined the effects of PGE2 stimulation on c⁃Maf expression and its downstream PI3K/AKT signaling pathway and analyzed the role of this pathway in PGE2⁃induced c⁃Maf expression using a PI3K inhibitor.

Results

Both mRNA microarray and proteomic data indicated that c⁃Maf knockout significantly altered multiple critical pathways in macrophages

especially those related to membrane

phagocytosis and cytoskeletal remodeling. Additionally

PGE2 upregulated c⁃Maf expression via the PI3K/AKT pathway

reducing macrophage phagocytic activity and promoting F⁃actin reorganization. The PI3K inhibitor significantly suppressed PGE2⁃induced c⁃Maf upregulation

highlighting the central regulatory role of PI3K/AKT signaling in this process.

Conclusion

This study demonstrates that PGE2 upregulates c⁃Maf expression to reduce macrophage phagocytic capacity and cytoskeletal remodeling

a process mediated by the activation of the PI3K/AKT signaling pathway. The critical role of c⁃Maf in macrophage function regulation provides a potential therapeutic target for immune modulation and cancer immunotherapy.

关键词

Keywords

references

GUILLIAMS M , THIERRY G R , BONNARDEL J , et al . Establishment and maintenance of the macrophage niche [J ] . Immunity , 2020 , 52 ( 3 ): 434 ‑ 451 .

VEGA‑PÉREZ A , VILLARRUBIA L H , GODIO C , et al . Resident macrophage‑dependent immune cell scaffolds drive anti‑bacterial defense in the peritoneal cavity [J ] . Immunity , 2021 , 54 ( 11 ): 2578 ‑ 2594.e5 .

BARREBY E , AOUADI M . To be or not to be a hepatic niche macrophage [J ] . Immunity , 2022 , 55 ( 2 ): 198 ‑ 200 .

LI M , YANG Y , XIONG L , et al . Metabolism, metabolites, and macrophages in cancer [J ] . J Hematol Oncol , 2023 , 16 ( 1 ): 80 .

ZHANG X , JI L , LI M O . Control of tumor‑associated macrophage responses by nutrient acquisition and metabolism [J ] . Immunity , 2023 , 56 ( 1 ): 14 ‑ 31 .

KLOOSTERMAN D J , AKKARI L . Macrophages at the interface of the co‑evolving cancer ecosystem [J ] . Cell , 2023 , 186 ( 8 ): 1627 ‑ 1651 .

PUTTOCK E H , TYLER E J , MANNI M , et al . Extracellular matrix educates an immunoregulatory tumor macrophage phenotype found in ovarian cancer metastasis [J ] . Nat Commun , 2023 , 14 : 2514 .

KÉPES Z , DÉNES N , KERTÉSZ I , et al . Overview of prostaglandin E2 (PGE2)‑targeting radiolabelled imaging probes from preclinical perspective: Lessons learned and road ahead [J ] . Int J Mol Sci , 2023 , 24 ( 8 ): 6942 .

ZHANG T T , ZHANG C C , LI X , et al . Inflammation assessment and therapeutic monitoring based on highly sensitive and multi‑level electrochemical detection of PGE2 [J ] . Biosens Bioelectron , 2024 , 262 : 116539 .

KISHISHITA S , USUI‑OUCHI A , OUCHI Y , et al . Proliferative diabetic retinopathy microenvironment drives microglial polarization and promotes angiogenesis and fibrosis via cyclooxygena se‑2/prostaglandin E2 signaling [J ] . Int J Mol Sci , 2024 , 25 ( 20 ): 11307 .

ROY S , ROY S , BANERJEE M , et al . Antileishmanial activity of cathelicidin and its modulation by Leishmania donovani in a cAMP response element modulator‑dependent manner in infection [J ] . J Infect Dis , 2024 , 230 ( 1 ): 172 ‑ 182 .

SANTISO A , HEINEMANN A , KARGL J . Prostaglandin E2 in the tumor microenvironment, a convoluted affair mediated by EP receptors 2 and 4 [J ] . Pharmacol Rev , 2024 , 76 ( 3 ): 388 ‑ 413 .

PUNYAWATTHANANUKOOL S , MATSUURA R , WONGCHANG T , et al . Prostaglandin E2‑EP2/EP4 signaling induces immunosuppression in human cancer by impairing bioenergetics and ribosome biogenesis in immune cells [J ] . Nat Commun , 2024 , 15 : 9464 .

VLEESHOUWERS W , VAN DEN DRIES K , DE KEIJZER S , et al . Characterization of the signaling modalities of prostaglandin E2 receptors EP2 and EP4 reveals crosstalk and a role for microtubules [J ] . Front Immunol , 2020 , 11 : 613286 .

HILLION S , MIRANDA A , LE DANTEC C , et al . Maf expression in B cells restricts reactive plasmablast and germinal center B cell expansion [J ] . Nat Commun , 2024 , 15 : 7982 .

ALVAREZ‑MARTINEZ M , COX L S , PEARSON C F , et al . Blimp‑1 and c‑Maf regulate immune gene networks to protect against distinct pathways of pathobiont‑induced colitis [J ] . Nat Immunol , 2024 , 25 : 886 ‑ 901 .

CHANG Y , BACH L , HASIUK M , et al . TGF‑β specifies T FH versus T H 17 cell fates in murine CD4 + T cells through c‑Maf [J ] . Sci Immunol , 2024 , 9 ( 93 ): eadd4818 .

BROCKMANN L , TRAN A , HUANG Y M , et al . Intestinal microbiota‑specific Th17 cells possess regulatory properties and suppress effector T cells via c‑MAF and IL‑10 [J ] . Immunity , 2023 , 56 ( 12 ): 2719 ‑ 2735.e7 .

LIU M , TONG Z , DING C , et al . Transcription factor c‑Maf is a checkpoint that programs macrophages in lung cancer [J ] . J Clin Invest , 2020 , 130 ( 4 ): 2081 ‑ 2096 .

MINEMATSU H , AFIFY S M , SUGIHARA Y , et al . Cancer stem cells induced by chronic stimulation with prostaglandin E2 exhibited constitutively activated PI3K axis [J ] . Sci Rep , 2022 , 12 : 15628 .

YAZDIMAMAGHANI M , KOLUPAEV O V , LIM C , et al . Tumor microenvironment immunomodulation by nanoformulated TLR 7/8 agonist and PI 3 k delta inhibitor enhances therapeutic benefits of radiotherapy [J ] . Biomaterials , 2025 , 312 : 122750 .

BAMRA T , SHAFI T , DAS S , et al . Leishmania donovani secretory mevalonate kinase regulates host immune response and facilitates phagocytosis [J ] . Front Cell Infect Microbiol , 2021 , 11 : 641985 .

CUI H , LIU Y , ZHENG Y , et al . Intelectin enhances the phagocytosis of macrophages via CDC42‑WASF 2 ‑ARPC2 signaling axis in Megalobrama amblycephala [J ] . Int J Biol Macromol , 2023 , 236 : 124027 .

JOSHI S , LÓPEZ L , MOROSI L G , et al . Tim4 enables large peritoneal macrophages to cross‑present tumor antigens at early stages of tumorigenesis [J ] . Cell Rep , 2024 , 43 ( 4 ): 114096 .

MANTOVANI A , ALLAVENA P . The interaction of anticancer therapies with tumor‑associated macrophages [J ] . J Exp Med , 2015 , 212 ( 4 ): 435 ‑ 445 .

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