Regulatory roles of SP-A and exosomes in pneumonia-induced acute lung and kidney injuries.
Regulatory roles of SP-A and exosomes in pneumonia-induced acute lung and kidney injuries.
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DOI：
10.3389/fimmu.2023.1188023
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发表时间：
2023
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
--
作者：
肺炎诱导的脓毒症可引起多器官功能障碍，包括急性肺和肾损伤（ALI和阿基）。表面活性蛋白A（SP-A）是一种重要的先天性免疫分子，在肺和肾中表达。细胞外囊泡如外泌体参与病理生理过程。在这里，我们测试了一个假设，即SP-A通过调节外泌体和细胞死亡来调节肺炎诱导的阿基。在本研究中使用野生型（WT）、SP-A敲除（KO）和人源化SP-A转基因（hTG，肺特异性SP-A表达）小鼠。与WT和hTG小鼠相比，铜绿假单胞菌内感染后，KO小鼠显示死亡率增加，损伤评分更高，肺部和肾脏炎症更严重，血清TNF-α、IL-1β和IL-6水平升高。感染的hTG小鼠表现出类似的肺损伤，但比感染的WT小鼠更严重的肾损伤。与WT和hTG小鼠相比，发现KO小鼠肾脏中的肾小管凋亡和焦亡增加。我们发现，败血症小鼠的血清外泌体通过介导小鼠静脉注射时的细胞凋亡和突眼引起ALI和阿基。此外，在暴露于脓毒症血清外泌体后，从KO小鼠分离的原代近端肾小管上皮细胞显示出比来自WT小鼠的那些细胞更高的敏感性。总的来说，SP-A通过调节炎症、细胞凋亡和焦亡来减轻肺炎诱导的ALI和AKI;血清外泌体是阿基发病机制中的重要介质。
Pneumonia-induced sepsis can cause multiple organ dysfunction including acute lung and kidney injury (ALI and AKI). Surfactant protein A (SP-A), a critical innate immune molecule, is expressed in the lung and kidney. Extracellular vesicles like exosomes are involved in the processes of pathophysiology. Here we tested one hypothesis that SP-A regulates pneumonia-induced AKI through the modulation of exosomes and cell death. Wild-type (WT), SP-A knockout (KO), and humanized SP-A transgenic (hTG, lung-specific SP-A expression) mice were used in this study. After intratracheal infection with Pseudomonas aeruginosa, KO mice showed increased mortality, higher injury scores, more severe inflammation in the lung and kidney, and increased serum TNF-α, IL-1β, and IL-6 levels compared to WT and hTG mice. Infected hTG mice exhibited similar lung injury but more severe kidney injury than infected WT mice. Increased renal tubular apoptosis and pyroptosis in the kidney of KO mice were found when compared with WT and hTG mice. We found that serum exosomes from septic mice cause ALI and AKI through mediating apoptosis and proptosis when mice were injected intravenously. Furthermore, primary proximal tubular epithelial cells isolated from KO mice showed more sensitivity than those from WT mice after exposure to septic serum exosomes. Collectively, SP-A attenuates pneumonia-induced ALI and AKI by regulating inflammation, apoptosis and pyroptosis; serum exosomes are important mediators in the pathogenesis of AKI.
DOI：
10.1016/j.bbadis.2016.11.032
发表时间：
2017-02
影响因子：
6.2
作者：
Tian, Shaojiang;Li, Chenxiao;Ran, Ran;Chen, Shi-You
通讯作者：
Chen, Shi-You