Evidence map›Paper›PMID 33553322›Full record

ArticleAnnals of translational medicine2021

Macrophage-derived netrin-1 contributes to endometriosis-associated pain.

Shaojie Ding, Xinyue Guo, Libo Zhu, Jianzhang Wang, Tiantian Li, Qin Yu, Xinmei Zhang

Open access · diamondAbstract read
In one paragraph

Article in Annals of translational medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
3.1field-weighted citation impact, top 9% 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

22 citing papers in PubMed, 32 citations in OpenAlex.

  1. Review
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  6. MRGPRX2 Mediates Mast Cell-Induced Endometriosis Pain Through the Sensitization of Sensory Neurons via Histamine/HRH1/TRPV1 Signaling Pathway.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025
    Article
  7. Review
  8. Article
  9. Endometriosis: An Immunologist's Perspective.International journal of molecular sciences · 2025
    Review
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  12. Review
  13. Article
  14. Observational
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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

7 authors at 2 institutions in 1 country.

Shaojie DingDepartment of Gynecology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Xinyue GuoZhejiang University School of Medicine, Hangzhou, China.
Libo ZhuDepartment of Gynecology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Jianzhang WangDepartment of Gynecology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Tiantian LiZhejiang University School of Medicine, Hangzhou, China.
Qin YuDepartment of Gynecology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Xinmei ZhangDepartment of Gynecology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Women's Hospital, School of Medicine, Zhejiang University · CNZhejiang University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundEndometriosis-associated pain can be considered a type of neuropathic pain. Netrin-1 is an axon guidance cue that regulates axonal attraction or rejection in neural injury and regeneration. However, whether netrin-1 plays a role in endometriosis-associated pain remains unclear. This study aimed to determine the role of netrin-1 in endometriosis-related pain.

methodsPeripheral blood, peritoneal fluid, and endometrial tissues were sampled from women with (n=37) and without endometriosis (n=23). Lipopolysaccharide (LPS) and interferon gamma (IFN-γ) were used to stimulate human monocytic cell lines (THP-1) and rat alveolar macrophage-derived cell lines (NR8383) to induce M1 phenotype macrophages. Serum netrin-1 concentrations, endometrial expression levels of netrin-1, and its receptors including deleted in colorectal cancer (DCC), A2B adenosine receptor (A2BAR), uncoordinated B receptor (UNC5B), uncoordinated C receptor (UNC5C) and Down's syndrome cell adhesion molecule (DSCAM) were assessed. The polarization phenotypes of the peritoneal macrophages were identified by detecting the marker expression of M1/M2 macrophages via flow cytometry. The expression levels of M1 markers and netrin-1 in THP-1/NR8383 cells were determined.

resultsThe expression levels of netrin-1 in serum and endometriotic lesions were significantly higher in women with endometriosis, and were positively correlated with the severity of endometriosis-associated pain. Netrin-1 was co-expressed with CD68 (a macrophage marker) in endometriotic lesions and was synthesized and secreted by THP-1 and NR8383 cells in the process of M1 polarization. In women with endometriosis, peritoneal macrophages were polarized towards the M1 phenotype. In addition, increased expression of DCC and A2BAR, and decreased expression of UNC5B, UNC5C and DSCAM were found in endometriotic lesions.

conclusionsThese results suggest that netrin-1 production by macrophages in endometriotic lesions may play an important role in endometriosis-associated pain.

Indexed as

Endometriosismacrophagenetrin-1painpolarization

Identifiers

PMID33553322
PMCPMC7859736
OpenAlexW3108580235

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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.