Tianjin Nankai Hospital, Tianjin Medical University; Institute of Integrative Medicine for Acute Abdominal Diseases, Tianjin; Tianjin Key Laboratory of Acute Abdomen Disease Associated Organ Injury and ITCWM Repair.
Tianjin Nankai Hospital, Tianjin Medical University; Institute of Integrative Medicine for Acute Abdominal Diseases, Tianjin; Tianjin Key Laboratory of Acute Abdomen Disease Associated Organ Injury and ITCWM Repair.
Biochim Biophys Acta Mol Basis Dis. 2024 Dec;1870(8):167480. doi: 10.1016/j.bbadis.2024.167480. Epub 2024 Aug 30.
Electroacupuncture has been demonstrated to mitigate endotoxin-induced acute lung injury by enhancing mitochondrial function. This study investigates whether electroacupuncture confers lung protection through the regulation of mitochondrial quality control mediated by heme oxygenase-1 (HO-1) and the mitochondrial inner membrane protein MIC60. HO-1, an inducible stress protein, is crucial for maintaining mitochondrial homeostasis and protecting against lung injury. MIC60, a key component of the mitochondrial contact site and cristae organizing system, supports mitochondrial integrity. We employed genetic knockout/silencing and cell transfection techniques to model lipopolysaccharide (LPS)-induced lung injury, assessing changes in mitochondrial structure, reactive oxygen species (ROS) production, mitochondrial membrane potential (MMP), and the expression of proteins essential for mitochondrial quality control. Our findings reveal that electroacupuncture alleviates endotoxin-induced acute lung injury and associated mitochondrial dysfunction, as evidenced by reductions in lung injury scores, decreased ROS production, and suppressed expression of proteins involved in mitochondrial fission and mitophagy. Additionally, electroacupuncture enhanced MMP and upregulated proteins that facilitate mitochondrial fusion and biogenesis. Importantly, the protective effects of electroacupuncture were reduced in models with Hmox1 knockout or Mic60 silencing, and in macrophages transfected with Hmox1-siRNA or Mic60-siRNA. Moreover, HO-1 was found to influence MIC60 expression during electroacupuncture preconditioning and LPS challenge, demonstrating that these proteins not only co-localize but also interact directly. In conclusion, electroacupuncture effectively modulates mitochondrial quality control through the HO-1/MIC60 signaling pathway, offering an adjunctive therapeutic strategy to ameliorate endotoxin-induced acute lung injury in both in vivo and in vitro settings.
电针对内毒素诱导的急性肺损伤具有保护作用，其机制可能与增强线粒体功能有关。本研究旨在探讨电针对急性肺损伤的保护作用是否与血红素加氧酶-1（HO-1）和线粒体内膜蛋白 MIC60 介导的线粒体质量控制有关。HO-1 是一种诱导型应激蛋白，对于维持线粒体稳态和减轻肺损伤至关重要。MIC60 是线粒体接触点和嵴间空间组织系统的关键组成部分，对于维持线粒体的完整性具有重要作用。本研究采用基因敲除/沉默和细胞转染技术构建脂多糖（LPS）诱导的急性肺损伤模型，观察电针对急性肺损伤时线粒体结构、活性氧（ROS）产生、线粒体膜电位（MMP）以及线粒体质量控制相关蛋白表达的影响。结果显示，电针对 LPS 诱导的急性肺损伤具有保护作用，减轻肺损伤评分、减少 ROS 产生、下调线粒体分裂和自噬相关蛋白的表达，改善 LPS 诱导的急性肺损伤时的线粒体功能障碍。进一步研究发现，电针通过上调 HO-1 表达，增强 MMP 和促进线粒体融合、生物发生的相关蛋白的表达，发挥对 LPS 诱导的急性肺损伤的保护作用。Hmox1 敲除或 Mic60 沉默减弱了电针对 LPS 诱导的急性肺损伤的保护作用，同时，转染 Hmox1-siRNA 或 Mic60-siRNA 的巨噬细胞也降低了电针对 LPS 诱导的急性肺损伤的保护作用。此外，电针预处理和 LPS 刺激后 HO-1 表达增加，且与 MIC60 共定位并相互作用。综上所述，电针通过 HO-1/MIC60 信号通路有效调节线粒体质量控制，为 LPS 诱导的急性肺损伤提供了一种新的治疗策略。
