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定量蛋白质学揭示了PPAR信号通路调节新生小鼠心脏的心肌细胞活动

Xinyu Li¹, Nannan Wang¹, Minhui Gui¹

¹State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Key Laboratory of Molecular Medicine, Chemistry and Biomedicine Innovation Center, Medical School of Nanjing University, Nanjing, China.

|June 5, 2023

概括

了解心脏发育为治疗心血管疾病 (CVD) 提供了新的希望. 激活过氧体增殖器激活受体 (PPAR) 途径显示出增强心肌细胞活性和潜在治疗心血管疾病的前景.

科学领域:

蛋白质组学和心血管研究
心脏发育的分子机制

背景情况:

心血管疾病 (CVD) 是全球主要的死亡原因,目前的治疗方法有局限性.
小鼠心脏的产后发育,特别是高心肌细胞活性的窗口,为心血管疾病提供了潜在的治疗点.

研究的目的:

在小鼠中创建心脏发育的蛋白质图谱.
确定关键的分子变化和涉及心脏成熟的途径.
基于发育洞察力,探索对心血管疾病的潜在治疗策略.

主要方法:

使用iTRAQ的定量蛋白质学在从胚胎日18.5到产后8周的小鼠腹腔组织上进行.
分析确定了3422个量化蛋白质,并描述了心脏发育过程中的蛋白质组变化.
生物信息分析的重点是调节失调的蛋白质和丰富的信号通路.

主要成果:

建立了一份关于小鼠心脏发育的全面蛋白质图谱.
关键的发育事件,包括从糖解转变为β-氧化的代谢转变,以蛋白质组变化为特征.
确定了与心脏再生相关的显著失调的蛋白质 (例如Erbb2,Agrin,Hmgb) 和过氧体增殖器激活受体 (PPAR) 信号通路.

结论:

过氧体增殖器激活受体 (PPAR) 信号通路在心脏发育过程中得到显著丰富.
使用贝扎菲布拉特激活PPAR通路,通过增加Cpt1α表达来增强心肌细胞 (H9C2) 活性.
激活PPAR通路代表了治疗心血管疾病的潜在治疗策略.

关键词:

在PPAR信号通路中.贝扎菲布拉特是一种纤维化物.心脏发育的心脏发育心脏衰竭是因为心脏衰竭.定量化的蛋白质组学.

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