Exosomes of human adipose stem cells mitigate irradiation injury to salivary glands by inhibiting epithelial-mesenchymal transition through miR-199a-3p targeting Twist1 and regulating TGFβ1/Smad3 pathway
Bibliographic record
Abstract
Rationale: Currently, irradiation-injured salivary glands (IR-SG) lack effective clinical treatment options.Emerging treatments using exosomes (Exo) have shown promising outcomes for various diseases.However, the efficacy of exosome in treating IR-SG remains unexplored.This study aimed to use exosomes to restore IR-SG function and to explore their underlying mechanisms.Methods: Exosomes isolated from human adipose-derived stem cell (ADSC-Exo) were injected into C57BL/6 mice that had their salivary glands injured with 14Gy.RNA sequencing profiled differentially expressed miRNAs and mRNAs of IR-SG.Epithelial-mesenchymal transition (EMT) mechanisms were further examined using SMG-C6 cells.Results: Exo-treated mice had a 96% increase in saliva secretion, higher cell proliferation, upregulated tissue repair/regeneration genes, and preserved functional cells with fewer collagen fibers compared to saline-treated mice.Exo treatment increased the expression of epithelial cell markers while decreasing mesenchymal cell markers.Notably, miR-199a-3p was significantly upregulated in Exo-treated mice, promoting cell growth and reducing EMT.Twist1, an EMT transcription factor, was identified as a direct target of miR-199a-3p and confirmed by luciferase assays.Twist1 overexpression promoted EMT, but Exo treatment or Twist1 knockdown reduced EMT marker expression and inactivated the TGF1/Smad3 pathway.Conclusions: ADSC-Exo is a promising therapy for IR-SG, primarily by mitigating EMT through miR-199a-3p targeting Twist1 and regulating the TGF1/Smad3 pathway.
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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 | 0.000 | 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) | 0.000 | 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".