Platelet-Derived TGF (Transforming Growth Factor)-β1 Enhances the Aerobic Glycolysis of Pulmonary Arterial Smooth Muscle Cells by PKM2 (Pyruvate Kinase Muscle Isoform 2) Upregulation
| العنوان: | Platelet-Derived TGF (Transforming Growth Factor)-β1 Enhances the Aerobic Glycolysis of Pulmonary Arterial Smooth Muscle Cells by PKM2 (Pyruvate Kinase Muscle Isoform 2) Upregulation |
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| المؤلفون: | Ying Zhu, Dan Shu, Xue Gong, Meng Lu, Qinyu Feng, Xiang-Bin Zeng, Han Zhang, Jiahui Gao, Ya-Wei Guo, Luman Liu, Rong Ma, Liping Zhu, Qinghua Hu, Zhang-Yin Ming |
| المصدر: | Hypertension. 79:932-945 |
| بيانات النشر: | Ovid Technologies (Wolters Kluwer Health), 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Mammals, Pulmonary Arterial Hypertension, Hypertension, Pulmonary, Muscles, Myocytes, Smooth Muscle, Pyruvate Kinase, Pulmonary Artery, Vascular Remodeling, Rats, Up-Regulation, Transforming Growth Factor beta1, Mice, Internal Medicine, Animals, Protein Isoforms, Hypoxia, Glycolysis, Cell Proliferation, Signal Transduction |
| الوصف: | Background: Metabolic reprogramming is a hallmark of pulmonary arterial hypertension. Platelet activation has been implicated in pulmonary arterial hypertension (PAH), whereas the role of platelet in the pathogenesis of PAH remains unclear. Methods: First, we explored the platelet function of semaxanib‚ a inhibitor of VEGF receptor (SU5416)/hypoxia mice and monocrotaline-injected rats PAH model. Then we investigated pulmonary arterial smooth muscle cell aerobic glycolysis after being treated with platelet supernatant. TGF (transforming growth factor)-βRI, pyruvate kinase muscle 2, and other antagonists were applied to identify the underlying mechanism. In addition, platelet-specific deletion TGF-β1 mice were exposed to chronic hypoxia and SU5416. Cardiopulmonary hemodynamics, vascular remodeling, and aerobic glycolysis of pulmonary arterial smooth muscle cell were determined. Results: Here, we demonstrate that platelet-released TGF-β1 enhances the aerobic glycolysis of pulmonary arterial smooth muscle cells after platelet activation via increasing pyruvate kinase muscle 2 expression. Mechanistically, platelet-derived TGF-β1 regulate spyruvate kinase muscle 2 expression through mTOR (mammalian target of rapamycin)/c-Myc/PTBP-1(polypyrimidine tract binding protein 1)/hnRNPA-1(heterogeneous nuclear ribonucleoprotein A1) pathway. Platelet TGF-β1 deficiency mice are significantly protected from SU5416 plus chronic hypoxia–induced PAH, including attenuated increases in right ventricular systolic pressure and less pulmonary vascular remodeling. Also, in Pf4cre + Tgfb1 fl/fl mice, pulmonary arterial smooth muscle cells showed lower glycolysis capacity and their pyruvate kinase muscle 2 expression decreased. Conclusions: Our data demonstrate that TGF-β1 released by platelet contributes to the pathogenesis of PAH and further highlights the role of platelet in PAH. |
| تدمد: | 1524-4563 0194-911X |
| DOI: | 10.1161/hypertensionaha.121.18684 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::282157423c5c396aedfb6cf5a6ee5edb https://doi.org/10.1161/hypertensionaha.121.18684 |
| رقم الانضمام: | edsair.doi.dedup.....282157423c5c396aedfb6cf5a6ee5edb |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15244563 0194911X |
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| DOI: | 10.1161/hypertensionaha.121.18684 |