Cellular and Molecular Life Sciences CMLS

, Volume 60, Issue 8, pp 1716–1724

The agonist of the protease-activated receptor-1 (PAR1) but not PAR3 mimics thrombin-induced vascular endothelial growth factor release in human vascular smooth muscle cells

  • T. Arisato
  • K. P. Sarker
  • K. Kawahara
  • M. Nakata
  • T. Hashiguchi
  • M. Osame
  • I. Kitajima
  • I. Maruyama
Research Article

DOI: 10.1007/s00018-003-3140-6

Cite this article as:
Arisato, T., Sarker, K., Kawahara, K. et al. CMLS, Cell. Mol. Life Sci. (2003) 60: 1716. doi:10.1007/s00018-003-3140-6

Abstract

Thrombin, a serine protease generated by the activation of the blood coagulation cascade following vessel injury, induces vascular endothelial growth factor (VEGF) release. However, the molecular mechanism of thrombin-induced VEGF release is largely unknown. An agonist of protease-activated receptor-1 (PAR1), SFLLRNPNDKYEPF, mimicked thrombin-induced VEGF release in human vascular smooth muscle (HVSM) cells, as determined by enzyme-linked immunosorbent assay, reverse transcriptase-polymerase chain reaction, and Northern blotting. In contrast, the agonist of PAR3, TFRGAP, did not affect VEGF release or expression. SFLLRNPNDKYEPF, but not TFRGAP, up-regulated [Ca2+]i. Moreover, the calcium ionophone A23187 was found to trigger VEGF release in HVSM cells. Thrombin-induced VEGF release was blocked by anti-thrombin, heparin, a synthetic thrombin receptor inhibitor E5510, the calcium chelator BAPTA, the protein kinase C inhibitor calphostin C, and the MEK1/2 inhibitor U0126. Thus, our data show that thrombin caused VEGF release via PAR1 activation in a manner dependent on [Ca2+]i and p44/42 downstream from the receptor activation.

Thrombin HVSM cell PAR1 Ca2+ p44/42 VEGF 

Copyright information

© Birkhäuser-Verlag Basel 2003

Authors and Affiliations

  • T. Arisato
    • 1
    • 2
  • K. P. Sarker
    • 1
    • 2
  • K. Kawahara
    • 1
  • M. Nakata
    • 1
  • T. Hashiguchi
    • 1
  • M. Osame
    • 3
  • I. Kitajima
    • 4
  • I. Maruyama
    • 1
  1. 1.Department of Laboratory and Molecular MedicineFaculty of Medicine, Kagoshima UniversityKagoshima
  2. 2.Department of Cell Biology and AnatomyThe University of Calgary, Faculty of Medicine, 3330 Hospital Dr., NW, 383 Heritage Medical Research Building, T2N 4N1CalgaryAlberta
  3. 3.Third Department of Internal MedicineFaculty of Medicine, Kagoshima UniversityKagoshima
  4. 4.Department of Laboratory MedicineFaculty of Medicine, Toyama Medical and Pharmaceutical UniversityToyama

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