奥斯托邦丁在肺上皮质炎症和上皮质-白细胞相互作用中的调节作用
Huirong Fu1,2, Xuanqi Liu1,3, Lin Shi1
1Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital, Fudan University Shanghai Medical College, Shanghai, China.
Clinical and translational medicine
|August 22, 2023
概括
骨质前列腺素 (OPN) 通过影响上皮细胞及其与特洛细胞 (TCs) 的通信来调节肺炎和损伤. 控制肺上皮的OPN显示出治疗肺部疾病的前景.
科学领域:
- 肺部医学 肺部医学
- 细胞生物学 细胞生物学
- 免疫学 免疫学 免疫学
背景情况:
- 肺上皮细胞在炎症和损伤中至关重要,但机制尚不清楚.
- 骨质前列腺素 (OPN) 影响上皮损伤,修复和肺癌.
- 纤维细胞 (TCs) 与上皮细胞相互作用,以减轻肺炎和损伤.
研究的目的:
- 探索OPN如何调节源自上皮细胞的肺炎.
- 为了研究在急性和慢性肺损伤中上皮细胞和TC之间的相互作用.
- 阐明OPN在肺上皮质反应中的作用机制.
主要方法:
- 生物信息学定义了OPN和上皮炎症的肺病特异性.
- 评估了OPN在OPN淘汰/过度表达的支气管上皮质 (HBEs) 和OPN淘汰动物模型中的OPN的调节作用.
- 诱导的急性肺损伤和COPD使用吸烟或脂聚糖 (LPS).
- 评估了OPN对PI3K和ERK通路的影响.
- 利用空间转录学和共同培养系统来分析OPN,上皮亚型,TC及其相互作用.
主要成果:
- 在吸烟者,COPD患者以及COPD和肺癌患者中,OPN的表达增加.
- 在HBEs中LPS/CSE诱导的细胞因子过量产生,依赖于OPN功能障碍.
- 在OPN淘汰赛小鼠中,肺炎和损伤显著减少.
- 在HBEs中,OPN影响PI3K亚单元的表达.
- 空间分析显示,呼吸道表皮和TC之间的密切接触,由OPN介导.
结论:
- OPN调节肺上皮质炎症,损伤和上皮和TCs之间的细胞间通信.
- 肺上皮质OPN的有条件控制为预防和治疗上皮质起源的肺炎和损伤提供了潜在的策略.
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