在心肌梗塞后,Junctophilin-2 调节存储运行的进入心脏纤维细胞激活,纤维修复和血管生成
Jinxi Wang1, Daniela Sarahi Yang Bennett1, Emma J Echard1
1Abboud Cardiovascular Research Center, Division of Cardiovascular Medicine, Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, IA. (J.W., D.S.Y.B., E.J.E., B.C., W.Z., Q.S., J.-Y.Y., R.M.W., C.E.G., D.D.H., B.L., L.-S.S.).
对心脏纤维细胞功能和心脏损伤后的修复至关重要. 失去Jph2会影响的处理,纤维细胞的激活,并促进心脏的逆转型,突出显示其在心肌修复中的作用.
科学领域:
- 心血管生物学
- 细胞信号传输
- 纤维细胞生物学
背景情况:
- 心脏纤维细胞 (CFs) 通过 (Ca2+) 稳态来调节心肌损伤后的修复和重塑.
- 克托菲林-2 (JPH2) 是心肌细胞中已知的Ca2+信号调节剂,但其在CF中的作用尚不清楚.
研究的目的:
- 研究心脏纤维细胞中Junctophilin-2 (Jph2) 的表达和功能.
- 阐明Jph2在CF处理,激活和对心脏损伤的反应中的作用.
主要方法:
- 通过qPCR,西式涂抹和免疫光测试人类和小鼠CF中的Jph2表达.
- 使用活细胞Ca2+成像,RNA测序和TGFβ刺激在Jph2缺乏的CF中.
- 使用纤维细胞特异性的Jph2敲除小鼠 (Jph2 fKO) 来评估心脏功能,心肌梗塞后的重塑和血管生成.
主要成果:
- 在心肌梗塞后,Jph2是唯一的junctophilin.
- 在TGFβ治疗后,CF中的Jph2缺乏会影响激活,减少细胞外基质的产生,减少VEGF的表达.
- 在Jph2绝杀小鼠中,表现出心脏重塑的恶化,静脉缩功能障碍,血管生成受损,心肌梗塞后心肌纤维扩散的改变.
- Jph2与Stim1相互作用,调节储存的Ca2+输入和TGFβ信号通路.
结论:
- Jph2对于CF的平衡,激活和细胞外基质的产生至关重要.
- 在心脏病发作中促进血管生成.
- 在心肌损伤后,Jph2作为心脏修复的中心调节者.
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