The Role and Regulation of Insulin-Like Growth Factor Binding Protein-4 in the Rodent Intestinal Mucosa
Bibliographic record
Abstract
Insulin-like growth factor-1 (IGF-1), epidermal growth factor (EGF) and glucagon-like peptide-2 (GLP-2) are all hormones that induce intestinal mucosal proliferation and growth. They are also interdependent as GLP-2 relies on IGF-1 and EGF to act as intermediary factors, which in turn act synergistically on the intestinal epithelium to stimulate proliferation. IGF binding protein-4 (IGFBP-4) regulates the activity of IGF-1 and is expressed highly in the intestine. IGFBP-4 can inhibit IGF-1 activity, but also promotes IGF-1-induced growth in a protease-dependent manner in whole body and bone. However, the role of IGFBP-4 within the intestine is not well defined. Thus, I hypothesized that IGFBP-4 is required for the growth promoting effects of GLP-2, which require the actions of IGF-1, but inhibits basal intestinal epithelial proliferation. Because the intestinal growth factors stimulate Sox9 expression, a transcriptional promoter for IGFBP-4, I also hypothesized that mucosal IGFBP-4 expression is stimulated by GLP-2, IGF-1, and EGF. GLP-2-treated control mice displayed increased intestinal weight per body weight, crypt-villus height and epithelial proliferation while the IGFBP-4 knockout (KO) mice had impaired increases in all of these parameters. In contrast, vehicle-treated IGFBP-4 KO mice had elevated intestinal weight per body weight, crypt-villus height, and epithelial proliferation compared to vehicle-treated control mice. Consistently, IGFBP-4 dose-dependently decreased IEC-6 cell proliferation in an IGF-1 receptor (IGF-1R)- and MEK1/2-dependent manner. Finally, chronic GLP-2 treatment in vivo increased mucosal IGFBP-4 mRNA expression. However, chronic inhibition of EGFR and/or intestinal epithelial IGF-1R KO in vivo did not alter mucosal IGFBP-4 expression. Altogether, the results demonstrate that IGFBP-4 is integral for promoting GLP-2-induced mucosal growth and inhibiting growth under basal conditions and that mucosal IGFBP-4 expression is regulated in a GLP-2-dependent but not IGF-1/EGF-dependent manner.
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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 | 0.001 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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 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".