在高葡萄糖下通过IGTAV/FAK通路进行肝鼻状毛细化
Jia Liu1,2, Hengjiang Gong3, Jinxing Quan2
1The First Clinical College of Lanzhou University, Lanzhou, 730000, Gansu province, China.
Applied biochemistry and biotechnology
|June 29, 2023
概括
患有非酒精性脂肪性肝病 (NAFLD) 的糖尿病患者的高葡萄糖增加了整合蛋白αv (IGTAV) 和FAK信号,导致肝脏的鼻状毛细体. 沉默IGTAV通过减少关键蛋白质表达来改善这种情况.
科学领域:
- 肝病学和代谢疾病
- 细胞和分子生物学 细胞和分子生物学
- 内皮细胞生物学 内皮细胞生物学
背景情况:
- 在全球范围内,非酒精性脂肪性肝病 (NAFLD) 的发病率正在上升,特别是在糖尿病患者中.
- 连接糖尿病和NAFLD的确切机制,特别是关于肝脏侧鼻内皮细胞的确切机制,仍然不清楚.
- 整合素,包括整合素αv (IGTAV),涉及到NAFLD的病原性.
研究的目的:
- 调查整合素αv (IGTAV) /FAK通路在高葡萄糖诱导的糖尿病NAFLD患者肝脏鼻状毛细化中的作用.
- 在高血糖条件下探索涉及IGTAV,拉米林 (LN) 和FAK信号的特定分子机制.
主要方法:
- 人类肝脏侧鼻内皮细胞 (HLSECs) 被培养和鉴定.
- 使用定量实时PCR (qRT-PCR) 和lentivirus载体来使IGTAV基因沉默.
- 在高葡萄糖 (25 mmol/L) 和对照 (曼尼托尔) 条件下,西式涂抹和扫描电子显微镜评估了蛋白质表达 (IGTAV,LN,FAK,-FAK) 和细胞变化.
主要成果:
- 高葡萄糖显著上调IGTAV,LN和-FAK蛋白表达在HLSECs.
- 在早期时间点 (2h, 6h) 上,IGTAV基因沉默有效抑制了-FAK和LN表达.
- 在高葡萄糖条件下,抑制IGTAV和FAK信号传递降低了LN表达,改善了肝脏鼻状毛细体.
结论:
- 高葡萄糖通过IGTAV/FAK通路诱导糖尿病的NAFLD患者的肝侧侧毛细化.
- 针对IGTAV/FAK通路提供了一种潜在的治疗策略,以减轻糖尿病NAFLD中高葡萄糖诱导的肝损伤.
- 了解这些分子相互作用对于开发糖尿病NAFLD的有效治疗方法至关重要.
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