Research Paper|Volume 13, Issue 9|pp 12466—12478

Supplementary research on K150del variant of activated protein C

Wen-Yi Lin¹, Liang Tang¹, Xuan Lu¹, Yu Hu¹

¹Institute of Hematology, Union Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

* Equal contribution

Received: October 8, 2020Accepted: March 13, 2021Published: April 25, 2021

https://doi.org/10.18632/aging.202904

Copyright: © 2021 Lin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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).