Abstract 17326: Blockade of Thrombospondin1 Attenuates Tgfβ Signaling and Enhances the Automaticity of Tbx18-Induced Pacemaker Cells
العنوان: | Abstract 17326: Blockade of Thrombospondin1 Attenuates Tgfβ Signaling and Enhances the Automaticity of Tbx18-Induced Pacemaker Cells |
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المؤلفون: | Hee Cho, Natasha Fernandez, Jinqi Fan |
المصدر: | Circulation. 142 |
بيانات النشر: | Ovid Technologies (Wolters Kluwer Health), 2020. |
سنة النشر: | 2020 |
مصطلحات موضوعية: | Cell physiology, Cell signaling, business.industry, Genetic enhancement, Automaticity, Cell biology, Blockade, Extracellular matrix, Transcriptome, Physiology (medical), Medicine, Cardiology and Cardiovascular Medicine, business, Transcription factor |
الوصف: | Introduction: Transcription factor Tbx18 can reprogram chamber cardiomyocytes to induced pacemaker cells (iPMs). Transcriptomic analysis of Tbx18-iPMs identified Tgfβ pathway as a prominent signaling cascade in this transition. The activity of Tgfβ1 is regulated primarily in the extracellular domain where the secreted latent form must be modified to expose the active ligand. We hypothesize that thrombospondin1 (Tsp1) mediates the activation of the Tgfβ signaling by Tbx18. Methods: Neonatal rat ventricular myocytes (NRVMs) were transduced with adenoviral constructs expressing either human TBX18 or GFP. Results: Tsp1 transcript (Thbs1) level was higher in TBX18 iPMs compared to GFP-NRVMs (1.5±1.3 vs 0.6±0.6, p Conclusions: Our data identify Tsp1 as the key mediator through which Tbx18 activates the Tgfβ pathway during iPM reprogramming. Inhibition of Tgfβ pathway may serve as a solution to attain durable pacing from TBX18-iPMs. |
تدمد: | 1524-4539 0009-7322 |
URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::694ba84c37ac6a14254b70899109da57 https://doi.org/10.1161/circ.142.suppl_3.17326 |
رقم الأكسشن: | edsair.doi...........694ba84c37ac6a14254b70899109da57 |
قاعدة البيانات: | OpenAIRE |
تدمد: | 15244539 00097322 |
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