Schistosoma japonicum peptide SJMHE1 promotes peripheral nerve regeneration via macrophage migrasome-derived miR-26b-5p targeting the PTEN/AKT axis
Bibliographic record
Abstract
BACKGROUND: Peripheral nerve injury (PNI) is a major clinical challenge with limited effective therapeutic options. Our prior work has demonstrated that SJMHE1, a peptide derived from Schistosoma japonicum, promotes peripheral nerve regeneration by regulating M2 macrophages; however, its downstream molecular mechanisms remain unclear. Migrasomes are newly identified migration-dependent extracellular vesicles that mediate intercellular communication, and are abundantly produced by highly migratory macrophages. The present study investigates whether SJMHE1 promotes peripheral nerve regeneration through macrophage-derived migrasomes, with a focus on the role of these migrasomes in macrophage-Schwann cell crosstalk. METHODS: The formation of migrasomes was observed using an in vivo rat model of sciatic nerve transection injury and in vitro macrophage-Schwann cell co-culture systems. SJMHE1-induced macrophage-derived migrasomes (SM-M) were systematically characterized: transmission electron microscopy (TEM) for morphological analysis, nanoparticle tracking analysis (NTA) for size distribution, and Western blotting (WB) for detecting migrasome marker proteins (e.g., TSPAN4, PIGK). The regulatory effects of SM-M on Schwann cell function were evaluated using multiple approaches: CCK-8 and EdU assays to assess cell proliferation, Transwell assays to measure cell migration in vitro; and a rat sciatic nerve crush injury model to verify in vivo regenerative effects (via immunofluorescence staining for S100 and NF200). Additionally, miRNA sequencing was performed on SM-M to identify key miRNAs and subsequent bioinformatics analysis was conducted to elucidate the potential molecular mechanisms by which SM-M regulates Schwann cell function. RESULTS: SJMHE1 treatment significantly enhances migrasome production in macrophages under both the in vivo and in vitro conditions. Functional experiments revealed that SM-M improve Schwann cell function in vivo and significantly promote the proliferation and migration of Schwann cells in vitro. Mechanistically, SM-M deliver miR-26b-5p to directly target and inhibit PTEN expression, thereby activating the AKT signaling pathway to regulate Schwann cell proliferation and migration. CONCLUSION: Our findings reveal a novel mechanism by which SJMHE1 promotes peripheral nerve regeneration through macrophage-Schwann cell communication mediated by miRNA delivery via macrophage migrasomes. This study highlights SJMHE1 as a promising therapeutic peptide for PNI and indicates that targeting migrasome-mediated communication between macrophages and Schwann cells may represent a new therapeutic strategy for PNI.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".