SNAIL Mediates TGF-β1–Induced Downregulation of Pentraxin 3 Expression in Human Granulosa Cells
Bibliographic record
Abstract
Transforming growth factor-β (TGF-β) 1 plays a critical role in regulating follicular development, and its dysregulation has been shown to be involved in the pathogenesis of ovulation dysfunction. SNAIL is a well-known transcriptional repressor that mediates TGF-β1-induced cellular functions. Pentraxin 3 (PTX3) is a key enzyme for the assembly and stabilization of the cumulus oophorus extracellular matrix, which is essential for cumulus expansion during the periovulatory stage. The purpose of the present study was to investigate the roles of TGF-β1 and SNAIL in the regulation of PTX3 expression and to examine the underlying mechanism. An established immortalized human granulosa cell (GC) line (SVOG), a GC tumor cell line (KGN), and primary human granulosa-lutein cells were used as study models. We demonstrated that TGF-β1 treatment substantially decreased the messenger RNA and protein levels of PTX3. This suppressive effect was abolished by cotreatment with the soluble TGF-β type II receptor (TβRII) or the ALK4/5/7 inhibitor SB431542. Knockdown of ALK5, SMAD2/3, or SMAD4 reversed the effects of TGF-β1-induced SNAIL upregulation and PTX3 suppression. These results indicate that TGF-β1 upregulates SNAIL and downregulates PTX3 expression via a TβRII-ALK5-mediated SMAD-dependent signaling pathway in human GCs. Additionally, TGF-β1-induced PTX3 suppression was mediated by upregulation of the SNAIL transcription factor, as knockdown of SNAIL completely reversed the suppression of PTX3 in response to TGF-β1. These findings could inform the roles of TGF-β1 and SNAIL in the regulation of follicular function and might provide therapeutic targets for the treatment of ovulation dysfunction.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| 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) | 0.002 | 0.001 |
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 source (direct Gemma or distilled Codex), 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".