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与 Grb2 相关的适应蛋白 GRAP 是肝纤维化的新型调节剂

Xiaoyan Wu¹, Yuwen Zhu², Yan Guo³

¹School of Sports and Health, Nanjing Sport Institute, Nanjing, China.

|June 21, 2023

概括

与Grb2相关的适应蛋白 (GRAP) 通过激活肝星细胞 (HSCs) 来促进肝纤维化. 在小鼠中抑制GRAP减少了肝纤维化,这表明GRAP是肝病的治疗标.

科学领域:

肝病学和分子生物学
细胞生物学细胞生物学

背景情况:

肝纤维化是慢性肝病的标志,导致肝功能受损.
肝星细胞 (HSC) 是肝纤维化的关键参与者,分化为肌纤维细胞.
Grb2相关适应蛋白 (GRAP) 在HSC激活和肝纤维化中的作用需要阐明.

研究的目的:

研究GRAP在肝星细胞激活中的作用.
确定GRAP在肝纤维化病原发生中的作用.

主要方法:

在小鼠中使用四化碳 (CCl4) 诱导的肝纤维化.
定量PCR和EDU结合试验用于基因表达和细胞增殖.
染色体免疫沉 (ChIP) 来评估DNA-蛋白相互作用.
在体外和体内使用小干扰RNA (siRNA) 和腺相关病毒6 (AAV6) 来抑制GRAP的研究.

主要成果:

在HSC向肌纤维细胞过渡期间,GRAP的表达增加.
血清反应因子 (SRF) 和肌肉相关的转录因子A (MRTF-A) 复合体激活了GRAP转录.
在体外,GRAP沉默抑制了HSC激活.
在体内减弱的肝纤维化.
过度表达GRAP增强了HSC激活,这被ERK信号抑制所取消.

结论:

GRAP调节HSC-肌纤维细胞过渡,可能通过ERK激活.
GRAP有助于肝纤维化的发展.
用小分子抑制剂向GRAP是一种潜在的肝纤维化治疗策略.

关键词:

肝脏的星状细胞.肝脏纤维化肝脏纤维化在MAPK信号传输中.肌纤维母细胞细胞.转录法规转录法规

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