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活化蛋白 C 的 K150del 变异体的补充研究。

Supplementary research on K150del variant of activated protein C.

机构信息

Institute of Hematology, Union Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

出版信息

Aging (Albany NY). 2021 Apr 25;13(9):12466-12478. doi: 10.18632/aging.202904.

DOI:10.18632/aging.202904
PMID:33896796
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8148483/
Abstract

Activated protein C (APC) is an anticoagulant with potent cytoprotective and anti-inflammatory effects. K150del, a natural variant of APC, is associated with reduced anticoagulant activity. We performed a comprehensive study to analyze the functional alterations of the K150del mutant. Transcriptome analysis of HEK 293T cells treated with wild and mutant APC revealed differentially expressed genes enriched in inflammatory, apoptotic, and virus defense-related signaling pathways. Both wild and mutant APC displayed concentration-dependent cytoprotective effects. Low concentrations of K150del mutant resulted in decreased anti-inflammatory and anti-apoptotic activities, whereas its higher concentrations restored these effects. Expression of virus defense-related genes improved in mouse lung tissues after repeated administration of the APC variant. These results suggest that the APC K150del mutant could help clinicians to accurately predict disease risks and serve as a potential auxiliary therapeutic in viral infections, including 2019 coronavirus disease (COVID-19).

摘要

活化蛋白 C（APC）是一种具有强大的细胞保护和抗炎作用的抗凝剂。APC 的一种天然变异 K150del 与抗凝活性降低有关。我们进行了一项全面的研究，以分析 K150del 突变体的功能改变。用野生型和突变型 APC 处理的 HEK 293T 细胞的转录组分析显示，炎症、凋亡和病毒防御相关信号通路中富集了差异表达的基因。野生型和突变型 APC 均显示出浓度依赖性的细胞保护作用。低浓度的 K150del 突变体导致抗炎和抗凋亡活性降低，而较高浓度的 K150del 突变体则恢复了这些作用。在反复给予 APC 变体后，小鼠肺组织中病毒防御相关基因的表达得到改善。这些结果表明，APC K150del 突变体可以帮助临床医生准确预测疾病风险，并作为病毒感染的潜在辅助治疗方法，包括 2019 年冠状病毒病（COVID-19）。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d585/8148483/099c02daa7d8/aging-13-202904-g007.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d585/8148483/7cef52e07840/aging-13-202904-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d585/8148483/cd7b3c1c1559/aging-13-202904-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d585/8148483/099c02daa7d8/aging-13-202904-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d585/8148483/790e009d7f7e/aging-13-202904-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d585/8148483/49aadc8c7e6f/aging-13-202904-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d585/8148483/99f19d7dda7d/aging-13-202904-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d585/8148483/634da6a29ffd/aging-13-202904-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d585/8148483/7cef52e07840/aging-13-202904-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d585/8148483/cd7b3c1c1559/aging-13-202904-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d585/8148483/099c02daa7d8/aging-13-202904-g007.jpg

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本文引用的文献

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J Thromb Haemost. 2020 May;18(5):1027-1038. doi: 10.1111/jth.14756. Epub 2020 Mar 5.
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Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China.中国武汉地区 2019 年新型冠状病毒感染患者的临床特征。
Lancet. 2020 Feb 15;395(10223):497-506. doi: 10.1016/S0140-6736(20)30183-5. Epub 2020 Jan 24.
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IFITM3 and type I interferons are important for the control of influenza A virus replication in murine macrophages.
IFITM3 和 I 型干扰素对于控制鼠源巨噬细胞中甲型流感病毒的复制非常重要。
Virology. 2020 Jan 15;540:17-22. doi: 10.1016/j.virol.2019.11.003. Epub 2019 Nov 5.
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Protein C Deficiency.蛋白 C 缺乏症。
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A key anti-viral protein, RSAD2/VIPERIN, restricts the release of measles virus from infected cells.一种关键的抗病毒蛋白，RSAD2/VIPERIN，限制麻疹病毒从受感染细胞中的释放。
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