通过TAOK1调节YAP/TEAD通路,作为心力衰竭中潜在的治疗点
Jiani Zhou1, Chaoqun Wu1, Miaohui Zhao1
1Department of General Practice, Ningbo Medical Treatment Center Li Huili Hospital, Affiliated to Ningbo University, Ningbo, Zhejiang, China.
介质素-17 (IL-17) 促进心肌细胞灭,并阻碍其增殖. 陶氏激酶1 (TAOK1) 通过调节NLRP3炎症体和YAP/TEAD通路来减轻这些影响.
科学领域:
- 心脏病学 心脏病学
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 介质蛋白-17 (IL-17) 与心血管疾病有关.
- 心肌细胞灭和扩散在心力衰竭中至关重要.
- 在这些过程中,TAO激酶1 (TAOK1) 和NLRP3炎症酶的作用需要阐明.
研究的目的:
- 调查IL-17,TAOK1和NLRP3在心肌细胞烧灭和增殖中的作用.
- 探索TAOK1在IL-17引起的心脏功能障碍中的调节机制.
- 在心力衰竭模型中评估调节这些途径的治疗潜力.
主要方法:
- 利用IL-17治疗的H9C2细胞作为体外心力衰竭模型.
- 操纵TAOK1表达 (过度表达/敲击) 并使用NLRP3炎症酶调节器 (BMS-986299,MCC950) 和YAP抑制剂 (脊椎蛋白).
- 评估了pyroptosis,增殖,基因/蛋白质表达和心肌病理 in vitro 和 doxorubicin 诱导的 HF 鼠标模型.
主要成果:
- IL-17增加了心肌细胞烧灭和减少了增殖,激活了NLRP3炎症体并抑制了YAP/TEAD通路.
- 过度表达TAOK1减轻了IL-17的影响,而敲击则加剧了它们.
- 在大鼠中,TAOK1过度表达减少了心肌损伤,并抑制了NLRP3炎症酶激活,恢复了YAP/TEAD通路活性.
结论:
- TAOK1是IL-17诱导的心肌细胞灭和增殖的关键调节者.
- TAOK1通过调节NLRP3炎症酶和YAP/TEAD通路活动来发挥其作用.
- 准TAOK1可能为心力衰竭提供治疗策略.
更多相关视频
11:32Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter
Published on: March 27, 2020
05:15Viral Transgene Expression in Rodent Hearts and the Assessment of Cardiac Arrhythmia Risk
Published on: July 27, 2022
相关概念视频
Transducer Mechanism: Enzyme-Linked Receptors
Major types that are helpful drug targets include:
Treatment for Pulmonary Arterial Hypertension: Receptor Tyrosine Kinase Inhibitors and Calcium Channel Blockers
TKIs, such as imatinib (Gleevec), are particularly effective in tackling the growth and mitogenic factors that become upregulated in PAH patients. These factors contribute to the...
Heart Failure Drugs: Inhibitors of Renin-Angiotensin System
Regulation of Angiogenesis and Blood Supply
PI3K/mTOR/AKT Signaling Pathway
Heart Failure Drugs: Inotropic Agents
