Thrombomodulin functions as a plasminogen receptor to modulate angiogenesis

Po Ku Chen, Bi Ing Chang, Cheng Hsiang Kuo, Pin Shern Chen, Chia Fong Cho, Chuan Fa Chang, Guey Yueh Shi, Hua Lin Wu

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

Urokinase-type plasminogen activator (uPA) activates plasminogen (Plg) through a major pericellular proteolytic system involved in cell migration and angiogenesis; however, the Plg receptor that participates in uPA-mediated Plg activation has not yet been identified. In this study, we demonstrated that thrombomodulin (TM), a type I transmembrane glycoprotein, is a novel Plg receptor that plays a role in pericellular proteolysis and cell migration. Plg activation at the cell surface and the extent of its cell migration- and invasion-promoting effect are cellular TM expression dependent. Direct binding of Plg and the recombinant TM extracellular domain, with a KD of 0.1 - 0.3 μM, was determined through surface plasmon resonance analysis. Colocalization of TM, Plg, and the uPA receptor within plasma membrane lipid rafts, at the leading edge of migrating endothelial cells, was demonstrated and was also shown to overlap with areas of major pericellular proteolysis. Moreover, the roles of TM and Plg in neoangiogenesis were demonstrated in vivo through the skin wound-healing model. In conclusion, we propose that TM is a novel Plg receptor that regulates uPA/uPA receptor-mediated Plg activation and pericellular proteolysis within lipid rafts at the leading edge of migrating cells during angiogenesis.

Original languageEnglish
Pages (from-to)4520-4531
Number of pages12
JournalFASEB Journal
Volume27
Issue number11
DOIs
Publication statusPublished - 2013 Nov

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Fingerprint Dive into the research topics of 'Thrombomodulin functions as a plasminogen receptor to modulate angiogenesis'. Together they form a unique fingerprint.

Cite this