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Published on: December 21, 2014
Thrombomodulin functions as a plasminogen receptor to modulate angiogenesis
Po-Ku Chen1, Bi-Ing Chang, Cheng-Hsiang Kuo
11Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, No. 1, University Rd., Tainan 701, Taiwan. H.-L.W., halnwu@mail.ncku.edu.tw.
Summary
Thrombomodulin (TM) is identified as a novel plasminogen (Plg) receptor crucial for urokinase-type plasminogen activator (uPA)-mediated cell migration and angiogenesis. TM facilitates Plg activation on cell surfaces, promoting cell movement and invasion.
Area of Science:
- Biochemistry
- Cell Biology
- Molecular Medicine
Background:
- Urokinase-type plasminogen activator (uPA) activates plasminogen (Plg) in pericellular proteolysis, a process vital for cell migration and angiogenesis.
- The specific plasminogen receptor involved in uPA-mediated activation remained unidentified.
Purpose of the Study:
- To identify the plasminogen receptor involved in urokinase-type plasminogen activator-mediated pericellular proteolysis.
- To elucidate the role of this receptor in cell migration, invasion, and angiogenesis.
Main Methods:
- Surface plasmon resonance was used to determine the binding affinity between plasminogen and thrombomodulin.
- Immunofluorescence microscopy was employed to visualize the colocalization of thrombomodulin, plasminogen, and uPA receptor in endothelial cells.
- In vivo studies using a skin wound-healing model assessed the roles of thrombomodulin and plasminogen in neoangiogenesis.
Main Results:
- Thrombomodulin (TM) was identified as a novel plasminogen (Plg) receptor, directly binding Plg with high affinity.
- Cellular TM expression levels correlated with Plg activation and enhanced cell migration and invasion.
- TM, Plg, and uPA receptor colocalized in lipid rafts at the leading edge of migrating endothelial cells, coinciding with pericellular proteolysis.
- In vivo, TM and Plg were shown to be important for neoangiogenesis during skin wound healing.
Conclusions:
- Thrombomodulin (TM) functions as a novel plasminogen (Plg) receptor, regulating uPA/uPA receptor-mediated Plg activation.
- TM is critical for pericellular proteolysis within lipid rafts, supporting cell migration and angiogenesis.
- This finding reveals a new mechanism regulating pericellular proteolysis and cell motility in biological processes like wound healing.
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