Heme Oxygenase Improves Renal Function by Potentiating Podocyte-Associated Proteins in <i>N</i>ω-Nitro-<scp>l</scp>-Arginine-Methyl Ester (<scp>l</scp>-NAME)-Induced Hypertension
Bibliographic record
Abstract
BACKGROUND: Although heme-oxygenase (HO) is cytoprotective, its effects on podocyte regulators like podocalyxin, podocin, CD2-associated protein (CD2AP) in renal dysfunction in N (ω)-nitro-l-arginine-methyl ester (l-NAME) hypertension are largely unclear. METHODS: Hypertension was induced in normotensive Sprague Dawley rats by administering l-NAME for 4 weeks. Enzyme immunoassay, enzyme-linked immunosorbent, histology/morphology, spectrophotometry, and western immunoblotting were used. HO was enhanced with heme-arginate (HA) or inhibited with chromium mesoporphyrin (CrMP). RESULTS: Treatment with heme-arginate reduced several renal histo-pathological lesions including renal arteriolar thickening, glomerular abnormalities, tubular cast, tubular atrophy/fibrosis, and mononuclear cell infiltration in l-NAME-hypertensive rats. Similarly, HA abated the elevated levels of renal extracellular matrix/profibrotic proteins like collagen and fibronectin that deplete nephrin, a fundamental transmembrane protein that forms the scaffoldings of the podocyte slit diaphragm permitting small ions to filter, but not massive excretion of proteins, hence proteinuria. Correspondingly, HA enhanced the aberrant expression of nephrin alongside other important regulators of podocyte like podocalyxin, podocin, and CD2AP, and improved renal function by reducing albuminuria/proteinuria, while increasing creatinine clearance. The renoprotection by HA were accompanied by significant reduction of inflammatory/oxidative mediators including nuclear factor-kappaB, macrophage inflammatory protein-1-alpha, macrophage chemoattractant protein-1, tumor necrosis factor-alpha, interleukin (IL)-6, IL1β, 8-isoprostane, endothelin-1, and aldosterone. These were associated with increased levels of adiponectin, HO-1, HO activity, cyclic guanosine monophosphate, and atrial natriuretic peptide (ANP), whereas the HO inhibitor, CrMP annulled the renoprotection and exacerbated renal dysfunction. CONCLUSIONS: HA improves renal function by attenuating histopathological lesions, suppressing inflammatory/oxidative mediators, abating profibrotic/extracellular matrix proteins, and reducing albuminuria/proteinuria, while concomitantly potentiating the HO-adiponectin-ANP axis, enhancing nephrin, podocin, podocalyxin, CD2AP and increasing creatinine clearance. Our study underscores the benefit of potentiating the HO-adiponectin-ANP against nephropathy.
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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) | 0.001 | 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".