Evidence map›Paper›PMID 40605618›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025

Cathepsin K Aggravates Pulmonary Fibrosis Through Promoting Fibroblast Glutamine Metabolism and Collagen Synthesis.

Mengting Chen, Xiaoxiao Meng, Yong Zhu, Dapeng Wang, Mengmeng Wang, Ziyuan Wang, Xue Tian, Jiaxiang Zhang, Zhiying Yue, Zhengfeng Yang and 1 more

Abstract read
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing 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

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

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

14 citing papers in PubMed.

  1. Article
  2. Glutamine metabolism in health and disease.Signal transduction and targeted therapy · 2026
    Review
  3. Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Review
  9. Article
  10. Review
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  12. 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

11 authors.

Mengting ChenDepartment of Critical Care Medicine, Shanghai General Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, 201620, China.
Xiaoxiao MengDepartment of Critical Care Medicine, Shanghai General Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, 201620, China.
Yong ZhuDepartment of Critical Care Medicine, Shanghai General Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, 201620, China.
Dapeng WangDepartment of Intensive Medicine, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, Jiangsu, 214023, China.
Mengmeng WangDepartment of Critical Care Medicine, Shanghai General Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, 201620, China.
Ziyuan WangPrecision Research Center for Refractory Diseases, Shanghai Jiao Tong University Pioneer Research Institute for Molecular and Cell Therapies, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201620, China.
Xue TianDepartment of Critical Care Medicine, Shanghai General Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, 201620, China.
Jiaxiang ZhangDepartment of Critical Care Medicine, Shanghai General Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, 201620, China.
Zhiying YuePrecision Research Center for Refractory Diseases, Shanghai Jiao Tong University Pioneer Research Institute for Molecular and Cell Therapies, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201620, China.
Zhengfeng YangDepartment of Critical Care Medicine, Shanghai General Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, 201620, China.
Ruilan WangDepartment of Critical Care Medicine, Shanghai General Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, 201620, China.ORCID https://orcid.org/0000-0001-9555-2649

Funding

Clinical Research Plan of SHDC SHDC2020CR5010-003Key Supporting Discipline of Shanghai Healthcare System 2023ZDFC0102National Key Clinical Specialty Discipline Construction Program of China Z155080000004National Key Research and Development Project 2020YFA0112900National Natural Science Foundation of China 81971555National Natural Science Foundation of China 82072210National Natural Science Foundation of China 82272645National Natural Science Foundation of China 82372987Natural Science Foundation of Shanghai 23ZR1451800Science and Technology Research Project from the Shanghai Songjiang District Science and Technology Commission 21SJKJGG32Shanghai Municipal Health Commission 2022YQ065Shanghai Rising-Star Program 23QA1408100
6 · The paper itself

Abstract

Fibroblast collagen synthesis is a hallmark of the pathogenesis and progression of pulmonary fibrosis (PF). However, the factors that trigger the abnormal activation of fibroblasts in PF are still not well understood. Using proteomics and single-cell sequencing dataset screening, extra accumulation of Cathepsin K (CTSK) is detected in the periphery as well as in fibroblasts in the lungs of PF mouse models. Addition of recombinant CTSK (rCTSK) aggravates collagen accumulation and PF progression in bleomycin-induced PF mice. Mechanically, CTSK underwent endocytosis through interaction with sorting nexin 9 (SNX9), which is engaged in TGF-β1 induced SMAD3 activation for downstream glutaminase 1 (GLS1) upregulation and glutamine enrichment. In turn, extra glutamine increases collagen synthesis in fibroblasts. More significantly, serum CTSK levels positively correlated with glutamine levels and poor prognosis in patients with PF. Thus, the results identify CTSK as a novel regulator of fibroblast activation that remodels glutamine metabolism and promotes collagen synthesis during PF pathogenesis. The correlation between peripheral CTSK and glutamine levels implies its future feasibility in the prediction and prevention of PF progression.

Indexed as

Cathepsin KCollagenFibroblastsGlutaminePulmonary FibrosisAnimalsBleomycinDisease Models, AnimalHumansMaleMiceMice, Inbred C57BLBleomycinCathepsin KCollagenGlutaminecollagen synthesisCTSKglutamine metabolismpulmonary fibrosisSNX9

Identifiers

PMID40605618
PMCPMC12442634

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.