Protease-Activated Receptor 4: A Critical Participator in Inflammatory Response

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• 作者：Qiang Fu (1)
  Jing Cheng (2)
  Yebo Gao (3)
  Yonglei Zhang (1)
  Xiaobing Chen (1)
  Jianguo Xie (1)
  
  1. Affiliated Cancer Hospital of Zhengzhou University ; Henan Cancer Hospital ; Zhengzhou ; 450008 ; China
  2. Zhengzhou Central Hospital Affiliated to Zhengzhou University ; Zhengzhou ; 450007 ; China
  3. Guang鈥檃nmen Hospital ; China Academy of Chinese Medical Science ; Beijing ; 100053 ; China
  
• 关键词：protease ; activated receptor 4 ; inflammation ; mechanisms ; coagulation
• 刊名：Inflammation
• 出版年：2015
• 出版时间：April 2015
• 年：2015
• 卷：38
• 期：2
• 页码：886-895
• 全文大小：261 KB
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• 刊物类别：Medicine
• 刊物主题：Medicine & Public Health
  Rheumatology
  Internal Medicine
  Pharmacology and Toxicology
  Pathology
  
• 出版者：Springer Netherlands
• ISSN：1573-2576

文摘

Protease-activated receptors (PARs) are G protein-coupled receptors of which four members PAR1, PAR2, PAR3, and PAR4 have been identified, characterized by a typical mechanism of activation involving various related proteases. The amino-terminal sequence of PARs is cleaved by a broad array of proteases, leading to specific proteolytic cleavage which forms endogenous tethered ligands to induce agonist-biased PAR activation. The biological effect of PARs activated by coagulation proteases to regulate hemostasis and thrombosis plays an enormous role in the cardiovascular system, while PAR4 can also be activated by trypsin, cathepsin G, the activated factor X of the coagulation cascade, and trypsin IV. Irrespective of its role in thrombin-induced platelet aggregation, PAR4 activation is believed to be involved in inflammatory lesions, as show by investigations that have unmasked the effects of PAR4 on neutrophil recruitment, the regulation of edema, and plasma extravasation. This review summarizes the roles of PAR4 in coagulation and other extracellular protease pathways, which activate PAR4 to participate in normal regulation and disease.