Endothelial derived miRNA-9 mediated cardiac fibrosis in diabetes and its regulation by ZFAS1
Bibliographic record
Abstract
Diabetic cardiomyopathy (DCM) is one of the most prevalent causes of morbidity and mortality in diabetic patients. Hyperglycemia induces increased expression/deposition of extracellular matrix (ECM) proteins including fibronectin (FN) and collagen (Col) and plays an important role in fibrosis in diabetic cardiomyopathy (DCM). The roles of RNAs including microRNA (miRNA) and long non-coding RNAs (lncRNA) have begun to be understood in many conditions. In this study, we investigated the role of a specific miRNA, miR-9, and its interactions with lncRNA ZFAS1 in mediating fibrosis in DCM. Treatment with 25 mM glucose (HG) decreased miR-9 expression and increased expressions of ZFAS1, ECM proteins and inflammatory markers, compared to 5 mM glucose (NG) in the HCMECs by using qRT-PCR. Glucose-induced upregulation of ECM proteins can be prevented by ZFAS1 siRNA or miR-9 mimic transfection. Luciferase assay was confirmed miR-9 binding to FN 3'-UTR. miR-9 expression can be regulated by ZFAS1 through polycomb repressive complex 2 (PRC2) components using RNA immunoprecipitation (RIP) and chromatin immunoprecipitation (ChIP) assays. In the in vivo experiment, hyperglycemia-induced the ECM production can be prevented by the miR-9 overexpression in the fibrosis in DCM. These studies showed a novel glucose-induced molecular mechanism in which ZFAS1 participates in the transcriptional regulation of ECM protein production in diabetes through miR-9.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| 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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".