Evidence map›Paper›PMID 25488667›Full record

ArticleThe Journal of biological chemistry2015

Matrix metalloproteinase-14 both sheds cell surface neuronal glial antigen 2 (NG2) proteoglycan on macrophages and governs the response to peripheral nerve injury.

Tasuku Nishihara, Albert G Remacle, Mila Angert, Igor Shubayev, Sergey A Shiryaev, Huaqing Liu, Jennifer Dolkas, Andrei V Chernov, Alex Y Strongin, Veronica I Shubayev

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed
2.8field-weighted citation impact, top 10% 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

40 citing papers in PubMed, 55 citations in OpenAlex.

  1. Article
  2. Article
  3. NG2 Glia and Cellular Crosstalk in Health and Disease: Focus on Spinal Cord Injury.Pathophysiology : the official journal of the International Society for Pathophysiology · 2026
    Review
  4. Review
  5. Article
  6. Emerging role of macrophages in neuropathic pain.Journal of orthopaedic translation · 2025
    Review
  7. Review
  8. Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. Review
  14. Proteolysis: a key post-translational modification regulating proteoglycans.American journal of physiology. Cell physiology · 2022
    Review
  15. Extracellular Matrix in Neural Plasticity and Regeneration.Cellular and molecular neurobiology · 2022
    Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. Review
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 at 4 institutions in 2 countries.

Tasuku NishiharaFrom the Departments of Anesthesiology, University of California, San Diego, La Jolla, California 92093, Veterans Affairs San Diego Healthcare System, La Jolla, California 92037, Department of Anesthesiology and Resuscitology, Ehime University, Toon, Ehime 791-0295, Japan.
Albert G RemacleSanford-Burnham Medical Research Institute, La Jolla, California 92037, and.
Mila AngertFrom the Departments of Anesthesiology, University of California, San Diego, La Jolla, California 92093, Veterans Affairs San Diego Healthcare System, La Jolla, California 92037.
Igor ShubayevVeterans Affairs San Diego Healthcare System, La Jolla, California 92037.
Sergey A ShiryaevSanford-Burnham Medical Research Institute, La Jolla, California 92037, and.
Huaqing LiuFrom the Departments of Anesthesiology, University of California, San Diego, La Jolla, California 92093, Veterans Affairs San Diego Healthcare System, La Jolla, California 92037.
Jennifer DolkasFrom the Departments of Anesthesiology, University of California, San Diego, La Jolla, California 92093, Veterans Affairs San Diego Healthcare System, La Jolla, California 92037.
Andrei V ChernovSanford-Burnham Medical Research Institute, La Jolla, California 92037, and.
Alex Y StronginSanford-Burnham Medical Research Institute, La Jolla, California 92037, and.
Veronica I ShubayevFrom the Departments of Anesthesiology, University of California, San Diego, La Jolla, California 92093, Veterans Affairs San Diego Healthcare System, La Jolla, California 92037, vshubayev@ucsd.edu.
Sanford Burnham Prebys Medical Discovery Institute · USVA San Diego Healthcare System · USUniversity of California, San Diego · USEhime University · JP

Funding

SAN DIEGO CLINICAL AND TRANSLATIONAL RESEARCH INSTITUTEUL1RR031980 · NCRR · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI FIRESTEIN, GARY S · 2010 to 2011
$14.0M
Proteolysis of Myelin as a Source of Neuropathic PainR01DE022757 · NIDCR · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SHUBAYEV, VERONICA · 2012 to 2022
$7.3M
Pathogenesis of Nerve Injury: Role of Tissue Inhibitor of Metalloproteinases-1 (TIMP-1)I01BX000638 · VA · VA SAN DIEGO HEALTHCARE SYSTEM · PI VERONICA SHUBAYEV · 2009 to 2026
–
BLRD VA I01 BX000638NCRR NIH HHS UL1 RR031980NIDCR NIH HHS R01 DE022757NIDCR NIH HHS R01DE022757
6 · The paper itself

Abstract

Neuronal glial antigen 2 (NG2) is an integral membrane chondroitin sulfate proteoglycan expressed by vascular pericytes, macrophages (NG2-Mφ), and progenitor glia of the nervous system. Herein, we revealed that NG2 shedding and axonal growth, either independently or jointly, depended on the pericellular remodeling events executed by membrane-type 1 matrix metalloproteinase (MT1-MMP/MMP-14). Using purified NG2 ectodomain constructs, individual MMPs, and primary NG2-Mφ cultures, we demonstrated for the first time that MMP-14 performed as an efficient and unconventional NG2 sheddase and that NG2-Mφ infiltrated into the damaged peripheral nervous system. We then characterized the spatiotemporal relationships among MMP-14, MMP-2, and tissue inhibitor of metalloproteinases-2 in sciatic nerve. Tissue inhibitor of metalloproteinases-2-free MMP-14 was observed in the primary Schwann cell cultures using the inhibitory hydroxamate warhead-based MP-3653 fluorescent reporter. In teased nerve fibers, MMP-14 translocated postinjury toward the nodes of Ranvier and its substrates, laminin and NG2. Inhibition of MMP-14 activity using the selective, function-blocking DX2400 human monoclonal antibody increased the levels of regeneration-associated factors, including laminin, growth-associated protein 43, and cAMP-dependent transcription factor 3, thereby promoting sensory axon regeneration after nerve crush. Concomitantly, DX2400 therapy attenuated mechanical hypersensitivity associated with nerve crush in rats. Together, our findings describe a new model in which MMP-14 proteolysis regulates the extracellular milieu and presents a novel therapeutic target in the damaged peripheral nervous system and neuropathic pain.

Indexed as

AnimalsAntigensAxonsCell MembraneCells, CulturedChondroitin Sulfate Proteoglycan 4Extracellular SpaceFemaleGAP-43 ProteinHEK293 CellsHumansLamininMacrophagesMaleMatrix Metalloproteinase 14Matrix Metalloproteinase 2AntigensChondroitin Sulfate Proteoglycan 4GAP-43 ProteinLamininMatrix Metalloproteinase 14Matrix Metalloproteinase 2Mmp2 protein, ratProteoglycansExtracellular MatrixMacrophageMatrix Metalloproteinase (MMP)MT1-MMPNerveNG2PainProteoglycanRegenerationSchwann Cells

Identifiers

PMID25488667
PMCPMC4319034
OpenAlexW2035317322

What OpenQuestion holds

Textmetadata
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.