Evidence mapPaperPMID 40640787Full record

ArticleRespiratory research2025

MTMR14 depletion aggravates intrapulmonary inflammation and emphysema in experimental COPD through activating macrophage M1 polarization.

Jiaheng Zhang, Yuan Zhan, Zhesong Deng, Shanshan Chen, Ruonan Yang, Yating Zhang, Hao Fu, Qian Huang, Jixing Wu, Yiya Gu and 1 more

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Article in Respiratory research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

11 authors.

Jiaheng Zhang *Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China.
Yuan Zhan *Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Zhesong DengDepartment of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China.
Shanshan ChenDepartment of Pulmonary and Critical Care Medicine, Fujian Provincial Hospital, Fuzhou, China.
Ruonan YangDepartment of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China.
Yating ZhangDepartment of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China.
Hao FuDepartment of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China.
Qian HuangDepartment of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China.
Jixing WuDepartment of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China.
Yiya GuDepartment of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China. guyiya0825@163.com.
Jungang XieDepartment of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China. xiejjgg@hotmail.com.

Funding

Leading talents of public health in Hubei Province 2022SCZ047National Natural Science Foundation of China 82170049Noncommunicable Chronic Diseases-National Science and Technology Major Project 2023ZD0506300Project of Key R&D Program in Hubei Province 2023BCB127
6 · The paper itself

Abstract

backgroundChronic obstructive pulmonary disease (COPD) is typically characterized by chronic airway inflammation and emphysema. Macrophage polarization plays an important role in COPD, while the precise molecules and mechanisms underpinning it have yet to be fully elucidated. Pulmonary decrease of myotubularin-related protein 14 (MTMR14) expression conduces to the progression of COPD in our prior publication, while the further analysis reveals the differential expression of MTMR14 in alveolar macrophages, whose function and related mechanisms are worth further research. Our study aims to investigate the role and mechanism of MTMR14 in macrophages of COPD.

methodsThe expression and potential role of MTMR14 in COPD macrophages was explored via bioinformatic analysis and clinical detection, as well as in vivo and vitro experiments. By constructing animal model with Mtmr14 knockout and cell model with the knockdown or over-expression of MTMR14, the effect of MTMR14 on polarization direction of macrophages and the related signaling pathways were elaborated. Indirect co-culture was performed to probe the influence of MTMR14 in the crosstalk between macrophages and alveolar epithelium. The regulation of ubiquitin-proteasome system on MTMR14 expression was investigated via (co-)immunoprecipitation and cycloheximide chase assay.

resultsBased on analysis from open-access single-cell sequencing data, MTMR14 was down-regulated in macrophages of COPD patients, which was confirmed in clinical specimens, animal and cell models. Meanwhile, MTMR14 was functionally enriched in inflammatory response and macrophage activation. Correspondingly, the knockout of MTMR14 aggravated the pulmonary function decline, emphysema, inflammation and pro-inflammatory macrophage polarization in mice exposed by cigarette smoke (CS). Mechanically, MTMR14 negatively regulated the M1 polarization of macrophages under CS extract (CSE)-stimulation through PI3K/Akt and NF-κB pathways. In addition, damage from macrophages on alveolar epithelium was intensified by the down-regulation of MTMR14 in the formation of emphysema. Finally, TRIM21 was found to down-regulate MTMR14 through ubiquitin-proteasome system in CSE-stimulated macrophages.

conclusionsOur findings underscore the mitigative role of MTMR14 on macrophage polarization towards pro-inflammatory phenotype, offering a promising target for prevention and intervention for COPD in clinical settings. CLINICAL TRIAL NUMBER: Not applicable.

Indexed as

Cell PolarityMacrophage ActivationMacrophages, AlveolarPneumoniaProtein Tyrosine Phosphatases, Non-ReceptorPulmonary Disease, Chronic ObstructivePulmonary EmphysemaAnimalsDisease Models, AnimalFemaleHumansMacrophagesMaleMiceMice, Inbred C57BLMice, KnockoutProtein Tyrosine Phosphatases, Non-ReceptorChronic obstructive pulmonary diseaseEmphysemaInflammationMacrophage polarizationMyotubularin-related protein 14

Identifiers

PMID40640787
PMCPMC12243240

What Socratic holds

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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.