SREBP‐1 Mediates Angiotensin II‐induced TGFβ Upregulation in Kidney Mesangial Cells
Bibliographic record
Abstract
Angiotensin II (Ang II) is a key determinant of the progression of kidney disease of diverse etiology. Mesangial cells (MC) contribute importantly to the accumulation of glomerular matrix proteins and hence glomerular sclerosis. We recently demonstrated a role for the transcription factor sterol regulatory element binding protein (SREBP‐1), best known for its regulation of lipid metabolism, in high glucose fibrotic responses in MC. Here we assessed whether it mediated Ang II profibrotic signaling. We found that Ang II induced generation of the mature transcription factor (mSREBP‐1) in a dose‐ and time‐dependent manner in primary MC. Transcriptional activation was confirmed. The chaperone SCAP and protease S1P, as well as signaling through the Ang II type 1 receptor and PI3K/Akt were required for SREBP‐1 activation. Endoplasmic reticulum (ER) stress was a central mediator of Ang II‐induced PI3K/Akt and SREBP‐1 activation. In uninephrectomized C57BL/6 mice, Ang II infusion for 1 week upregulated expression of glomerular SREBP‐1 and the ER stress chaperone GRP78. The profibrotic cytokine transforming growth factor beta (TGFβ) is a central mediator of glomerular sclerosis. Inhibition of either ER stress or SREBP‐1 in MC prevented Ang II‐induced TGFβ upregulation. SREBP‐1 is thus an important mediator of Ang II‐induced profibrotic signaling through its effects on TGFβ upregulation.
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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 | 0.001 |
| 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".