Evidence map›Paper›PMID 34513819›Full record

ArticleFrontiers in cell and developmental biology2021

Exosomes From M2 Macrophage Promote Peritendinous Fibrosis Posterior Tendon Injury via the MiR-15b-5p/FGF-1/7/9 Pathway by Delivery of circRNA-Ep400.

Yinxian Yu, Binbin Sun, Zhuoying Wang, Mengkai Yang, Zhi Cui, Subin Lin, Mingming Jin, Chengqing Yi

Open access · goldAbstract read
In one paragraph

Article in Frontiers in cell and developmental biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
3.6field-weighted citation impact, top 6% of its field
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

15 citing papers in PubMed, 22 citations in OpenAlex.

  1. The cellular basis of fibrotic tendon healing: now in higher definition.American journal of physiology. Cell physiology · 2026
    Review
  2. Epigenetic mechanisms in stem cell therapies for achilles tendinopathy.Frontiers in cell and developmental biology · 2025
    Review
  3. Review
  4. Article
  5. Identification of Periostin as a critical niche for myofibroblast dynamics and fibrosis during tendon healing.Matrix biology : journal of the International Society for Matrix Biology · 2024
    Article
  6. Review
  7. Article
  8. Review
  9. Review
  10. Review
  11. Review
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  13. Review
  14. Circular RNAs and Their Role in Exosomes.Frontiers in oncology · 2022
    Review
  15. Article
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

8 authors at 4 institutions in 1 country.

Yinxian YuDepartment of Orthopaedic Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Binbin SunDepartment of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Zhuoying WangDepartment of Orthopaedic Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Mengkai YangDepartment of Orthopaedic Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Zhi CuiDepartment of Orthopaedic Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Subin LinDepartment of Orthopedics, The Second Affiliated Hospital of Soochow University, Suzhou, China.
Mingming JinShanghai Key Laboratory of Molecular Imaging, Shanghai University of Medicine and Health Sciences, Shanghai, China.
Chengqing YiDepartment of Orthopaedic Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Shanghai Jiao Tong University · CNShanghai First People's Hospital · CNShanghai University of Medicine and Health Sciences · CNSoochow University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Achilles tendon rupture prognosis is usually unsatisfactory. After the tendon is injured, it may not function properly because of the fibrotic healing response, which restrains tendon motion. Inflammatory monocytes and tissue-resident macrophages are indispensable regulators in tissue repair, fibrosis, and regeneration. Exosomes from macrophages are crucial factors in tissue microenvironment regulation following tissue injury. This study therefore aimed to clarify the roles of macrophage exosomes in tendon injury (TI) repair. The results show that macrophages play a role after TI. M1 macrophages were increased relative to peritendinous fibrosis after TI. High-throughput sequencing showed abnormal expression of circular RNAs (circRNAs) between exosomes from M2 and M0 macrophages. Among the abnormal expressions of circRNA, circRNA-Ep400 was significantly increased in M2 macrophage exosomes. The results also show that M2 macrophage-derived circRNA-Ep400-containing exosomes are important for promoting peritendinous fibrosis after TI. Bioinformatics and dual-luciferase reporting experiments confirmed that miR-15b-5p and fibroblast growth factor (FGF)-1/7/9 were downstream targets of circRNA-Ep400. High circRNA-Ep400-containing exosome treatment inhibited miR-15b-5p, but promoted FGF1/7/9 expression in both fibroblasts and tenocytes. Furthermore, high circRNA-Ep400-containing exosome treatment promoted fibrosis, proliferation, and migration in both fibroblasts and tenocytes. Taken together, the results show that M2 macrophage-derived circRNA-Ep400-containing exosomes promote peritendinous fibrosis after TI via the miR-15b-5p/FGF-1/7/9 pathway, which suggests novel therapeutics for tendon injury treatment.

Indexed as

circRNA-Ep400exosomesFGF-1/7/9M2 macrophagemiR-15b-5ptendon injury

Identifiers

PMID34513819
PMCPMC8432299
OpenAlexW3197294898

What OpenQuestion holds

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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.