Recombinant BMP4 and BMP7 Downregulate Pentraxin 3 in Human Granulosa Cells
Bibliographic record
Abstract
CONTEXT: Theca cell-derived bone morphogenetic protein 4 (BMP4) and BMP7 are important regulators of folliculogenesis and have been shown to inhibit luteinization. Pentraxin 3 (PTX3) plays a critical role in the assembly of the cumulus oophorus extracellular matrix, which is essential for cumulus expansion during ovulation and may be modulated by BMP4 and BMP7. OBJECTIVE: The aim of this study was to investigate the effects of BMP4 and BMP7 on the expression of PTX3 in human granulosa cells and to examine their underlying molecular determinants. DESIGN: An established immortalized human granulosa cell line (SVOG), a granulosa cell tumor cell line (KGN), and primary granulosa-lutein cells were used as study models. PTX3 expression and accumulation as well as Smad1/5/8 phosphorylation were examined after exposure to recombinant human BMP4 and BMP7. BMP type I receptor involvement was investigated with inhibitors (dorsomorphin and DMH-1 (4-[6-[4-(1-Methylethoxy)phenyl]pyrazolo[1,5-a]pyrimidin-3-yl]-quinoline)) and small interfering RNAs targeting activin receptor-like kinase (ALK)2, ALK3, and/or ALK6. Small interfering RNAs targeting Smad4 were used to verify the involvement of Smad signaling. SETTING: The study was conducted at an academic research center. MAIN OUTCOME MEASURES: Quantitative RT-PCR and Western blot were used to measure mRNA and protein levels, respectively. Levels of PTX3 and BMP4 were measured by ELISA. RESULTS: Treatment with BMP4 and BMP7 significantly decreased PTX3 mRNA and protein production. These suppressive effects, along with the induction of Smad1/5/8 phosphorylation, were attenuated by cotreatment with 2 BMP type I receptor inhibitors (dorsomorphin and/or DMH-1). Combined knockdown (ALK3/ALK6 for BMP4 and ALK2/ALK3 for BMP7) reversed the effects of BMP4- and BMP7-induced Smad1/5/8 phosphorylation and PTX3 suppression. Furthermore, Smad4 knockdown reversed the suppressive effects of BMP4 and BMP7 on PTX3 expression. In follicular fluid, concentrations of PTX3 were negatively correlated with concentrations of BMP4. CONCLUSION: BMP4 and BMP7 use differential subsets of BMP type I receptors to downregulate PTX3 expression via Smad-dependent signaling in human granulosa cells.
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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".