A facultative plasminogen-independent thrombolytic enzyme from Sipunculus nudus

Mingqing Tang, Guoxing Ma, Chunyan Xu, Hui Yang, Hongjun Lin, Chao Bian, Chengjia Hu, Meiling Lu, Lei Chen, Wencai Jie, Zhen Yue, Jianbo Jian, Yuqing Sun, Hui Yan, Jingjing Zhou, Xianying Zhang, Shengye Liao, Zhaofa Li, Shuangfeng Cai, Yaqing Wu, Kexin Yang, Yanan Xiong, Yonggang Zhao, Zhimin Lv, Xiaoming Xu, Chuang Liu, Pengliang Xin, Lichao Ye, Xiuling Cui (), Qiong Shi (), Xi Chen () and Ruian Xu ()
Additional contact information
Mingqing Tang: Huaqiao University
Guoxing Ma: Huaqiao University
Chunyan Xu: BGI Research
Hui Yang: Northwest University
Hongjun Lin: Huaqiao University
Chao Bian: Shenzhen University
Chengjia Hu: Huaqiao University
Meiling Lu: Huaqiao University
Lei Chen: Huaqiao University
Wencai Jie: BGI Genomics
Zhen Yue: BGI Research
Jianbo Jian: BGI Genomics
Yuqing Sun: Huaqiao University
Hui Yan: Huaqiao University
Jingjing Zhou: Huaqiao University
Xianying Zhang: Huaqiao University
Shengye Liao: Huaqiao University
Zhaofa Li: Huaqiao University
Shuangfeng Cai: Huaqiao University
Yaqing Wu: Huaqiao University
Kexin Yang: Huaqiao University
Yanan Xiong: Huaqiao University
Yonggang Zhao: Huaqiao University
Zhimin Lv: Huaqiao University
Xiaoming Xu: Huaqiao University
Chuang Liu: The First Affiliated Hospital of Zhengzhou University
Pengliang Xin: Quanzhou First Hospital Affiliated to Fujian Medical University
Lichao Ye: Fujian Medical University
Xiuling Cui: Huaqiao University
Qiong Shi: Shenzhen University
Xi Chen: Northwest University
Ruian Xu: Huaqiao University

Nature Communications, 2025, vol. 16, issue 1, 1-19

Abstract: Abstract Current thrombolytic therapies primarily function by converting plasminogen into plasmin, a process dependent on the fibrin–activator complex. This dependence, coupled with the substantial molecular size of plasmin, constrains its effectiveness in degrading D-dimer and restricts its diffusion within thrombi. Here, we introduce a small facultative plasminogen-independent thrombolytic enzyme, snFPITE, isolated from Sipunculus nudus. Compared to traditional thrombolytic agents, snFPITE does not require plasminogen for thrombolysis, although its presence enhances lytic activity. This enzyme fully degrades cross-linked fibrin without leaving residual nondegradable D-dimer and generates a smaller fibrinolytic-active agent from plasminogen. A series of male rats and mice models further confirm that snFPITE is a safety injectable thrombolytic agent. Mechanistically, snFPITE activates plasminogen and degrades fibrin(ogen) in a multisite cleavage manner. snFPITE is inhibited by plasminogen activator inhibitor 1 and α2-antiplasmin via a competitive inhibition. We further identify 28 snFPITE candidate sequences, of which 10 are confirmed as functional genes.

Date: 2025
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DOI: 10.1038/s41467-025-58915-y

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