Insulin-like growth factor-binding protein-1 (IGFBP-1) mediates hypoxia-induced embryonic growth and developmental retardation
Why this work is in the frame
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Bibliographic record
Abstract
Although reduced fetal growth in response to hypoxia has been appreciated for decades, we have a poor understanding of the effects of hypoxia on embryonic development and the underlying cellular and molecular mechanisms. Here we show that hypoxia treatment not only resulted in embryonic growth retardation but also caused significant delay in developmental speed and the timing of morphogenesis in vital organs of zebrafish. Hypoxia strongly induced the expression of insulin-like growth factor (IGF)-binding protein (IGFBP)-1, a secreted protein that binds IGFs in extracellular environments. Hypoxia did not change the expression levels of IGFs, IGF receptors, or other IGFBPs. The hypothesis that elevated IGFBP-1 mediates hypoxia-induced embryonic growth retardation and developmental delay by binding to and inhibiting the activities of IGFs was tested by loss- and gain-of-function approaches. Knockdown of IGFBP-1 significantly alleviated the hypoxia-induced growth retardation and developmental delay. Overexpression of IGFBP-1 caused growth and developmental retardation under normoxia. Furthermore, reintroduction of IGFBP-1 to the IGFBP-1 knocked-down embryos restored the hypoxic effects on embryonic growth and development. When tested in vitro with cultured zebrafish embryonic cells, IGFBP-1 itself had no mitogenic activity, but it inhibited IGF-1- and IGF-2-stimulated cell proliferation. This inhibitory effect was abolished when IGF-1 or IGF-2 was added in molar excess, suggesting that IGFBP-1 inhibits embryonic growth and development by binding to and inhibiting the activities of IGFs. The induction of IGFBP-1 expression may be a conserved physiological mechanism to restrict the IGF-stimulated growth and developmental process under hypoxic stress.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.001 |
| 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 it