Abstract P2044: The Cardioprotective Egr-1 And Maladaptive Sp-1 Zinc Finger Transcription Factor Reciprocally Regulates Expression Of The Cardiomyocyte Performance Enhancing Protein S100a1
| Autor: | Martin Busch, Thien-Kim Bui, Lukas Adrian, Fabian Guenther, Mandy Rettel, Frank Stein, Jan Haas, Hagen Klett, Melanie Boerries, Benjamin Meder, Christoph Dieterich, Hugo A Katus, Patrick Most |
|---|---|
| Rok vydání: | 2022 |
| Předmět: | |
| Zdroj: | Circulation Research. 131 |
| ISSN: | 1524-4571 0009-7330 |
| Popis: | Background and Hypothesis: Expression of the cardiomyocyte (CM) protein S100A1, which improves contractile performance of the heart, sharply increases during postnatal myocardial maturation but declines rapidly in failing hearts. We therefore hypothesized that CMs are wired with transcriptional factors (TFs) that positively and negatively regulate S100A1’s gene locus activity. Understanding these reciprocal circuits may be relevant for advanced therapeutic modulation of S100A1’s abundance in diseased hearts. Methods and Results: H9C2 rat cardiomyoblasts, an animal-free in vitro tool, displayed a strong concordant rise in S100A1 mRNA and protein levels (8.1+/-1.1 vs. cont.; n=9, p2-fold enrichment over control were selected delivering EGR1 and SP1 as top hits. Subsequent siRNA-mediated silencing of both TFs yielded an EGR1 and SP1 knock-down dose-dependent inhibition (80%; p Conclusion: Our study identified the known cardioprotective EGR1 and maladaptive SP1 as novel positive and negative TF regulators of CM S100A1 expression and targets for therapeutic S100A1 gene locus modulation i.e., by SP1 TFBS gene-editing. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|