OS 25-03 OVEREXPRESSION OF HETEROGENEOUS NUCLEAR RIBONUCLEOPROTEIN F PREVENTS SYSTEMIC HYPERTENSION AND KIDNEY INJURY AND NORMALIZES RENAL RENIN-ANGIOTENSIN SYSTEM GENES EXPRESSION IN TYPE 2 DIABETIC DB/DB TRANSGENIC MICE
Bibliographic record
Abstract
Objective: We aimed to investigate whether overexpression of heterogeneous nuclear ribonucleoprotein F (HnRNP F, a transcription factor) in renal proximal tubular cells (RPTCs) prevents systemic hypertension and kidney injury in type 2 diabetic db/db transgenic (Tg) mice and study its underlying mechanism (s) of action. Design and Method: Db/db hnRNP F-Tg mice (BKS strain) were generated by cross-breeding of db/m + mice with Tg mice specifically overexpressing HnRNP F in their RPTCs using kidney-specific androgen-regulated protein promoter (KAP2). Adult (10–20 weeks of age) male wild type (WT), db/db and db/db HnRNP F- Tg mice were studied. Kidneys were processed for immunohistochemistry. Blood glucose (BG), systolic blood pressure (SBP) and urinary albumin/creatinine ratio (ACR) were monitored bi-weekly. Immunostaining, Western blotting and real-time qPCR were employed to assess angiotensinogen (AGT), angiotensin-converting enzyme (ACE), angiotensin-converting enzyme-2 (ACE-2), angiotensin 1–7 receptor (MasR), transforming growth factor-beta 1 (TGF-β1), Bax and active caspase-3 (Csp-3) protein expression and their mRNA levels in RPTCs, respectively. Rat immortalizaed RPTCs stably transfected with hnRNP F cDNA were studied in vitro. Results: Db/db mice exhibited increased BG, SBP and ACR as compared to WT mice. Db/db hnRNP F-Tg mice specifically overexpressing HnRNP F in their RPTCs attenuated these abnormalities except BG. AGT, ACE, TGF-β1, Bax and active Csp-3 protein and their respective mRNA expression in RPTCs were significantly increased whereas ACE2 and MasR 2 protein and mRNA were decreased in db/db mice compared to WT. These changes were normalized in db/db HnRNP F-Tg mice except ACE. In vitro, overexpression of HnRNP F inhibited AGT, TGF-β1, Bax and active Csp-3 protein and mRNA expression, whereas it increased ACE-2 and MasR expression in rat RPTCs. Conclusions: Our data suggest that intrarenal HnRNP F overexpression attenuates SBP, tubule-interstitial fibrosis and tubular apoptosis, predominantly through decreasing AGT and TGF-β1 expression and increasing ACE-2 and MasR expression.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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) | 0.002 | 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".