Evidence map›Paper›PMID 39972424›Full record

ArticleMolecular medicine (Cambridge, Mass.)2025

RTN3 regulates collagen biosynthesis and profibrotic macrophage differentiation to promote pulmonary fibrosis via interacting with CRTH2.

Chen-Yu Wang, Ya-Qin Chen, Hao Huang, Zhuang-Zhuang Yuan, Yi Dong, Jie-Yuan Jin, Jie-Yi Long, Lv Liu, Liang-Liang Fan, Rong Xiang

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular medicine (Cambridge, Mass.), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

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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

2 citing papers in PubMed.

  1. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Chen-Yu Wang *Department of Respiratory and Critical Care Medicine, Research Unit of Respiratory Disease of Central South University, Clinical Medical Research Center for Respiratory and Critical Care Medicine in Hunan Province, Diagnosis and Treatment Center of Respiratory Disease, The Second Xiangya Hospital, Central South University, Changsha, China.
Ya-Qin Chen *Department of Cell Biology, Hunan Key Laboratory of Medical Genetics, Hunan Key Laboratory of Animal Models for Human Disease, School of Life Sciences, Central South University, Changsha, China.
Hao HuangDepartment of Cell Biology, Hunan Key Laboratory of Medical Genetics, Hunan Key Laboratory of Animal Models for Human Disease, School of Life Sciences, Central South University, Changsha, China.
Zhuang-Zhuang YuanDepartment of Cell Biology, Hunan Key Laboratory of Medical Genetics, Hunan Key Laboratory of Animal Models for Human Disease, School of Life Sciences, Central South University, Changsha, China.
Yi DongDepartment of Cell Biology, Hunan Key Laboratory of Medical Genetics, Hunan Key Laboratory of Animal Models for Human Disease, School of Life Sciences, Central South University, Changsha, China.
Jie-Yuan JinDepartment of Cell Biology, Hunan Key Laboratory of Medical Genetics, Hunan Key Laboratory of Animal Models for Human Disease, School of Life Sciences, Central South University, Changsha, China.
Jie-Yi LongDepartment of Cell Biology, Hunan Key Laboratory of Medical Genetics, Hunan Key Laboratory of Animal Models for Human Disease, School of Life Sciences, Central South University, Changsha, China.
Lv LiuDepartment of Respiratory and Critical Care Medicine, Research Unit of Respiratory Disease of Central South University, Clinical Medical Research Center for Respiratory and Critical Care Medicine in Hunan Province, Diagnosis and Treatment Center of Respiratory Disease, The Second Xiangya Hospital, Central South University, Changsha, China. docliulv@csu.edu.cn.ORCID 0000-0001-9719-9930
Liang-Liang FanDepartment of Respiratory and Critical Care Medicine, Research Unit of Respiratory Disease of Central South University, Clinical Medical Research Center for Respiratory and Critical Care Medicine in Hunan Province, Diagnosis and Treatment Center of Respiratory Disease, The Second Xiangya Hospital, Central South University, Changsha, China. swfanliangliang@csu.edu.cn.ORCID 0000-0001-7431-1838
Rong XiangDepartment of Respiratory and Critical Care Medicine, Research Unit of Respiratory Disease of Central South University, Clinical Medical Research Center for Respiratory and Critical Care Medicine in Hunan Province, Diagnosis and Treatment Center of Respiratory Disease, The Second Xiangya Hospital, Central South University, Changsha, China. shirlesmile@csu.edu.cn.ORCID 0000-0002-5521-3615

Funding

National Natural Science Foundation of China 82000079National Natural Science Foundation of China 82170598National Natural Science Foundation of China 82300787National Natural Science Foundation of China 82470297Natural Science Foundation of Hunan Province 2021JJ40849Natural Science Foundation of Hunan Province 2022JJ30058Natural Science Foundation of Hunan Province 2023JJ20078
6 · The paper itself

Abstract

backgroundAs an endoplasmic reticulum (ER) protein, Reticulum 3 (RTN3) has been reported to play a crucial role in neurodegenerative diseases, lipid metabolism, and chronic kidney disease. The involvement of RTN3 in idiopathic pulmonary fibrosis (IPF), a progressive and fatal interstitial lung disease, remains unexplored.

methodsIn this study, we explored the role of RTN3 in pulmonary fibrosis using public datasets, IPF patient samples, and animal models. We investigated its pathogenic mechanisms in lung fibroblasts and alveolar macrophages.

resultsWe found decreased levels of RTN3 in IPF patients, bleomycin-induced mice, and TGFβ-treated cell lines. RTN3-null mice exhibited more severe pulmonary fibrosis phenotypes in old age or after bleomycin treatment. Collagen synthesis was significantly increased in RTN3-null mice lung tissues and lung fibroblasts. Mechanistic studies revealed that RTN3 deficiency reduced the ER-anchored CRTH2 in lung fibroblasts, which serves as an antifibrotic molecule via antagonizing collagen biosynthesis. Simultaneously, RTN3 deficiency reduced the autophagy degradation of CRTH2 which acts as an activator of profibrotic macrophage differentiation. Both effects of RTN3 and CRTH2 in lung fibroblasts and alveolar macrophages aggravated age-or bleomycin-induced pulmonary fibrosis. Additionally, we also identified a mutation of RTN3 in patients with ILD.

conclusionsOur research demonstrated that RTN3 plays a significant role in the lung, and reduction of RTN3 levels may be a risk factor for IPF and related diseases.

Indexed as

Cell DifferentiationCollagenIdiopathic Pulmonary FibrosisMacrophagesMembrane ProteinsNerve Tissue ProteinsPulmonary FibrosisAnimalsBleomycinCarrier ProteinsDisease Models, AnimalFibroblastsHumansMacrophages, AlveolarMiceMice, KnockoutBleomycinCarrier ProteinsCollagenMembrane ProteinsNerve Tissue ProteinsRTN3 protein, humanCollagen biosynthesisCRTH2Idiopathic pulmonary fibrosisIPFProfibrotic macrophage differentiationRTN3

Identifiers

PMID39972424
PMCPMC11837708

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Registered trials

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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 OpenQuestion graph.