Abstract 279: A Defective Mechanosensing Promotes Impaired Fibroblast-to-myofibroblast Maturation in the Aging Mouse Heart
| العنوان: | Abstract 279: A Defective Mechanosensing Promotes Impaired Fibroblast-to-myofibroblast Maturation in the Aging Mouse Heart |
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| المؤلفون: | Katarzyna A. Cieslik, Aude Angelini, JoAnn Trial |
| المصدر: | Circulation Research. 127 |
| بيانات النشر: | Ovid Technologies (Wolters Kluwer Health), 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | medicine.anatomical_structure, Physiology, Chemistry, medicine, macromolecular substances, Cardiology and Cardiovascular Medicine, Fibroblast, Myofibroblast, Mouse Heart, Cell biology |
| الوصف: | In the aging heart, fibroblasts have a reduced ability to mature into myofibroblasts (expressing contractile actin a-SMA), which is necessary for scar contraction in wound healing. The mechanosensing pathway bridges the extracellular matrix (ECM) with the actin cytoskeleton and is altered during aging. We emphasize that changes in this pathway may affect myofibroblast activation. Using various methods (mass spectrometry, qPCR, flow, IF staining, and western), we found several abnormalities in the fibroblasts derived from old mouse hearts: 1) ECM deposited was altered with an increased quantity of collagens and the presence of fibronectin variant Anastellin that opposes myofibroblast maturation; 2) there was a 50% reduction of Kindlin-2, a protein that promotes integrin activation; 3) Polymerized (F-) to monomeric (G-) actin ratio was decreased by 65%, possibly due to a 5-fold increase in pERKs1/2 level, a negative regulator of F-actin; and pERKs inhibition (by 2.5μM, PD-0325901) increased by 2-fold F/G actin ratio; 4) we found an increased cytoplasmic retention of MRTF-A (by 44%), an actin-sensitive co-transcription factor (necessary for a-SMA) that shuttles into the nucleus in response to F-actin formation; 5) pERKs inhibition increased a-SMA transcription by 78%. Thus, the disrupted mechanosensing pathway contributes to the impaired myofibroblast maturation in the aging heart. All experiments were performed in young (3-4 month-old) and old (24-30 month-old) hearts or primary cardiac fibroblasts isolated from male C57BL/6J mice. Unpaired Student’s t-test was used for statistical analysis, n=2 for mass spectrometry and n=4-10 for all other biological repeats. |
| تدمد: | 1524-4571 0009-7330 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::6e9908168548430dff257b1daab9e818 https://doi.org/10.1161/res.127.suppl_1.279 |
| رقم الأكسشن: | edsair.doi...........6e9908168548430dff257b1daab9e818 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15244571 00097330 |
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