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脓毒症诱导的肾上腺内皮微血管细胞激活与损伤的转录分析

Transcriptional Analysis of Sepsis-Induced Activation and Damage of the Adrenal Endothelial Microvascular Cells.

作者信息

Chen Lan-Sun, Singh Sumeet P, Müller Gregor, Bornstein Stefan R, Kanczkowski Waldemar

机构信息

Institute of Medical Microbiology and Hygiene, Technische Universität Dresden, Dresden, Germany.

Department of Internal Medicine III, University Hospital Carl Gustav Carus at the Technische Universität Dresden, Dresden, Germany.

出版信息

Front Endocrinol (Lausanne). 2020 Jan 22;10:944. doi: 10.3389/fendo.2019.00944. eCollection 2019.

Abstract

Bacterial sepsis is a serious threat to the body homeostasis and is often associated with high mortality in non-coronary intensive stations. In order to survive sepsis, rapid activation of the hypothalamus-pituitary-adrenal gland axis and sympathomedullary system is necessary. In many patients with sepsis, the function of those two arms of the stress system is dysregulated with underlying mechanisms remaining unknown. In our previous experimental studies, we have demonstrated that LPS-induced systemic inflammation and CLP-induced peritonitis can result in adrenal gland damage. Histological and transcriptomic analysis revealed a potential involvement of the adrenal microvascular endothelium in this process. However, our knowledge about the function of adrenal microvascular cells during sepsis is scarce. In the present study, we have characterized transcriptomic alterations in isolated mouse adrenal microvascular endothelial cells induced by systemic administration of bacterial LPS. Our results revealed that LPS induced a distinct transcriptomic profile in the adrenal microvascular cells, including multiple genes regulating inflammation, activation of the coagulation cascade and vascular permeability. Activation of those genes may be potentially involved in the damage to the microvascular endothelium and altogether contribute to the sepsis-mediated adrenal dysregulation.

摘要

细菌败血症对机体稳态构成严重威胁,在非冠状动脉重症监护病房常伴有高死亡率。为了在败血症中存活下来,下丘脑 - 垂体 - 肾上腺轴和交感髓质系统的快速激活是必要的。在许多败血症患者中,应激系统的这两个分支功能失调,其潜在机制尚不清楚。在我们之前的实验研究中,我们已经证明脂多糖诱导的全身炎症和盲肠结扎穿孔术诱导的腹膜炎可导致肾上腺损伤。组织学和转录组分析显示肾上腺微血管内皮可能参与了这一过程。然而,我们对败血症期间肾上腺微血管细胞功能的了解很少。在本研究中,我们对全身给予细菌脂多糖诱导的分离小鼠肾上腺微血管内皮细胞的转录组变化进行了表征。我们的结果显示,脂多糖在肾上腺微血管细胞中诱导了独特的转录组谱,包括多个调节炎症、凝血级联激活和血管通透性的基因。这些基因的激活可能潜在地参与微血管内皮的损伤,并共同导致败血症介导的肾上腺功能失调。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a882/6987315/7489531a1592/fendo-10-00944-g0001.jpg

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