154 Regulation of TGF-β and its Signaling Components by Oxygen Tension and Steroids in Skin Cells
Bibliographic record
Abstract
Inappropriate control of the expression and function of the components of the TGF-β signaling pathway has been implicated in impaired wound healing and abnormal scarring. Factors that have been shown to have profound effects on skin homeostasis and wound healing include steroids and oxygen tension. These agents may exert their effects (at least in part) on the skin and wound healing by modulating TGF-β action. To identify steroids and oxygen tension as mediators of TGF-β action in the skin, we examined the effects of hypoxia and glucocorticoids on the levels of active TGF-β and its signaling receptors and on the phosphorylation of its intracellular mediators, Smad 2 and Smad 3, in skin fibroblasts. Our results show that the active TGF-β levels, expression of types I and II receptors and phosphorylation of Smad2 and Smad3 are markedly up-regulated by 2 hrs of hypoxia, whereas all these parameters are significantly downregulated by 24 hrs of hypoxia. Dexamethasone treatment of 2 hrs, on the other hand, increased active TGF-β levels and TGF-β receptor expression with little effect on the levels of phosphorylated Smad2 and Smad3. However, dexamethasone treatment of 24 hrs downregulated the active TGF-β levels while maintaining the higher receptor expression, again with no significant effect on phosphorylated Smad2 and Smad3 levels. Interestingly, hypoxia had an additive effect on the steroid-induced downregulation of active TGF-β levels while counteracting the steroid-induced upregulation of TGF-β receptor expression. The upregulation at 2 hrs and the downregulation at 24 hrs of the components of TGF-β signaling pathway by hypoxia is consistent with the beneficial effect of initial hypoxia and the deleterious effect of sustained hypoxia, respectively, on wound healing. The synergestic and antagonistic effects of dexamethasone and hypoxia on the TGF-β signaling components emphasize the complex regulation of TGF-β signaling at multiple levels.
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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".