Abstract 032: Downregulation Of Trpm7 Is Associated With Inflammation And Fibrosis In Aldosterone-induced Hypertension
Bibliographic record
Abstract
Transient Receptor Potential Melastatin 7 (TRPM7) cation channel is a chanzyme (channel + kinase) that influences cellular Mg 2+ with an important role in cell homeostasis. Here, we investigated the importance of TRPM7-Mg 2+ in inflammatory response and oxidative stress in cardiac fibroblasts (CF) in the context of hypertension and organ damage induced by aldosterone and salt. Wild-type (WT) and TRPM7-deficient (M7+/Δ) mice were treated with aldosterone (600 μg/Kg/day) plus NaCl (1% drinking water), 4 weeks. Blood pressure (BP) was evaluated by tail cuff. Molecular mechanisms were investigated in primary culture of CF. Ca 2+ influx was assessed by fluorescence microscopy. Gene and protein expression was assessed by real-time PCR and immunoblotting respectively. M7+/Δ mice exhibited reduced TRPM7 expression (30%), phospho-TRPM7 (62%) and total tissue [Mg 2+ ] (28%). This was recapitulated in WT-aldo-salt. Aldo, salt and aldo-salt increased BP in M7+/Δ mice. In WT, only aldo-salt increased BP (134 mmHg). Cardiac collagen deposition (68%), expression of IL-6, TGFβ, p-Smad3 and p-ERK1/2 were increased (1.5-1.8 fold) in aldo-salt M7+/Δ versus WT. M7+/Δ CF exhibit increased mineralocorticoid target gene SGK1 (3-fold vs WT), which was increased by aldosterone (10-fold vs WT-aldo 5.4-fold). CF M7+/Δ had reduced aldosterone-induced calcium influx (peak-response 105±0.7 vs WT:149±10). CF M7+/Δ exhibited reduced proliferation (30%), and increases protein expression of TGFβ, IL-6, p-Smad3 and p-ERK1/2 (1.4-2.0-fold) vs WT. Nox2 (70%) and Nox4 (120%) expression was increased in CF M7+/Δ vs WT. Aldosterone increased Nox4 (54%) only in CF WT. These effects were associated with increased expression of oxidized peroxiredoxin-3 (76%). Increased gene expression for the antioxidant catalase (1.7-fold), NQO1 (2.6-fold) and Prdx1 (1.7-fold) was increased in M7+/Δ CF. Mg 2+ supplementation normalized intracellular [Mg 2+ ], cell proliferation, protein phosphorylation and Nox4 expression in CF TRPM7+/Δ (p<0.05). We identify a novel anti-inflammatory and anti-fibrotic role for TRPM7/Mg 2+ in cardiac fibroblasts. These processes are downregulated in aldo-induced hypertension.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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) | 0.004 | 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".