Lysophosphatidic acid stimulates thrombomodulin lectin-like domain shedding in human endothelial cells

Journal Article · Fri Feb 29 04:00:00 EST 2008 · Biochemical and Biophysical Research Communications

OSTI ID:21043638

Hualin, Wu ^[1]; ChiIou, Lin ^[2]; Yuanli, Huang ^[3]; Chen, Pin-Shern; Kuo, Cheng-Hsiang; Chen, Mei-Shing ^[1]; Wu, G C.-C. ^[3]; Shi, G -Y ^[1]; Yang, H -Y ^[3]; Hsinyu, Lee ^[2]

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1. Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan (China)
2. Institute of Zoology, National Taiwan University, Taipei 106, Taiwan (China)
3. Institute of Molecular and Cellular Biology, National Taiwan University, Taipei 106, Taiwan (China)

Thrombomodulin (TM) is an anticoagulant glycoprotein highly expressed on endothelial cell surfaces. Increased levels of soluble TM in circulation have been widely accepted as an indicator of endothelial damage or dysfunction. Previous studies indicated that various proinflammatory factors stimulate TM shedding in various cell types such as smooth muscle cells and epithelial cells. Lysophosphatidic acid (LPA) is a bioactive lipid mediator present in biological fluids during endothelial damage or injury. In the present study, we first observed that LPA triggered TM shedding in human umbilical vein endothelial cells (HUVECs). By Cyflow analysis, we showed that the LPA-induced accessibility of antibodies to the endothelial growth factor (EGF)-like domain of TM is independent of matrix metalloproteinases (MMPs), while LPA-induced TM lectin-like domain shedding is MMP-dependent. Furthermore, a stable cell line expressing TM without its lectin-like domain exhibited a higher cell proliferation rate than a stable cell line expressing full-length TM. These results imply that LPA induces TM lectin-like domain shedding, which might contribute to the exposure of its EGF-like domain for EGF receptor (EGFR) binding, thereby stimulating subsequent cell proliferation. Based on our findings, we propose a novel mechanism for the exposure of TM EGF-like domain, which possibly mediates LPA-induced EGFR transactivation.

• OSTI ID: 21043638
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 1 Vol. 367; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ANTIBODIES
ANTICOAGULANTS
CELL PROLIFERATION
DAMAGE
GLYCOPROTEINS
GROWTH FACTORS
LIPIDS
MUSCLES
RECEPTORS
VEINS