纤维细胞通过分泌肝细胞生长因子通过hexokinase 2-依赖途径保护肺组织纤维化
Shaoyuan Zhang1,2,3,4, Linyi Sun2,3,4, Borong Chen1
1Department of Thoracic Surgery, Zhongshan Hospital (Xiamen), Fudan University, Xiamen, China.
Clinical and experimental pharmacology & physiology
|September 16, 2023
概括
纤维细胞 (TCs) 通过释放肝细胞生长因子 (HGF) 来保护肺纤维化. 这个过程涉及到hexokinase 2 (HK2) 并减轻肺上皮质-介质细胞转化 (EMT).
科学领域:
- 细胞生物学 细胞生物学
- 肺部医学 肺部医学
- 再生医学是一种再生医学.
背景情况:
- 肺纤维化 (PF) 是肺移植后末期肺病和支气管炎消灭综合征 (BOS) 的标志.
- 肺上皮质-介质细胞转化 (EMT) 是肺组织纤维化的一个关键驱动因素.
- 纤维细胞 (TCs) 是已知在组织损伤时具有保护作用的介质细胞.
研究的目的:
- 为了研究TCs的抗纤维效应,在肺纤维化的老鼠气管上皮细胞 (RTE) 细胞模型中.
- 阐明潜在的机制,重点关注EMT,细胞代谢和肝细胞生长因子 (HGF) 的作用.
主要方法:
- 使用转化生长因子-β (TGF-β) 诱导RTE细胞进入纤维化状态.
- 与TC建立了共同培养系统,干预措施包括抗HGF抗体和基酶2 (HK2) 敲击.
- 使用的测试方法:西斑,海马XF分析仪,ELISA测量EMT标记,葡萄糖代谢 (乳酸盐,ATP) 和氧气消耗.
主要成果:
- 在RTE细胞中,TGF-β成功诱导肺纤维化和EMT.
- 在TC共同培养中,显著降低了EMT,乳酸盐,ATP生产和氧气消耗.
- TCs分泌HGF,用抗体阻断HGF逆转了抗纤维化的效果,这种效果被HK2敲击减弱.
结论:
- 在实验室中,TCs对肺组织纤维化具有保护作用.
- 这种保护作用是由HGF释放介导的,并且依赖于代谢酶HK2.2.
- 术疗法代表了缓解肺纤维化的潜在治疗策略,特别是在像BOS.这样的疾病中.
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