ER stress and a chronic inflammatory response are induced in an Angiotensin II/DOCA salt model of chronic kidney disease.
Bibliographic record
Abstract
We have developed a C57BL/6 mouse model of Chronic Kidney Disease (CKD). The mice underwent a uninephrectomy (Unx) or a sham operation. Unx mice received 1% NaCl in the drinking water and a 50 mg 21‐day release deoxycorticosterone (DOCA) pellet with Angiotensin II (AngII) infusion (1.5 ng Ang II/minute/g). Mice were sacrificed at day 21. This model produced CKD characterized by hypertensive proteinuria. We hypothesized that hypertension‐induced proteinuria results in endoplasmic reticulum (ER) stress as microarray studies in patients with established proteinuria showed upregulation of unfolded protein response (UPR) genes. In the model, electron microscopy showed disruption of the podocyte filtration barrier. Light microscopy revealed an increase in PAS‐positive intratubular protein casts. RT‐PCR analysis showed increased ER stress markers: GRP78, spliced XBP1, CHOP and TDAG51. TUNEL staining showed increased apoptosis in the tubular epithelium of Unx animals. An increase in T‐cell and macrophage infiltration confirmed an inflammatory response to CKD accompanied by renal interstitial fibrosis as shown by de novo α‐smooth muscle actin and collagen staining. This response may be due to ER stress induced pro‐inflammatory mediators such as NFκB. Future studies will assess whether the therapeutic inhibition of ER stress could alter the progression of chronic inflammation in CKD. Funding, CIHR OSO‐115895.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 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".