FSAP (Factor VII-activating protease) can cleave and inactivate PDGF-BB (platelet-derived growth factor-BB) and thereby inhibits VSMC (vascular smooth-muscle cell) proliferation. The auto-activation of FSAP is facilitated by negatively charged polyanions such as heparin, dextransulfate or extracellular ribonucleic acids. Since auto-activation is essential for the anti-proliferative function of FSAP, the influence of nucleic acids as cofactors for the FSAP-mediated inhibition of PDGF-BB was investigated. Natural or artificial RNA was an effective cofactor for FSAP mediated PDGF-BB degradation, whereas the effect of DNA was weak. RNA-induced cleavage of PDGF-BB was inhibited by serine protease inhibitors. The pattern of PDGF-BB cleavage was identical with either heparin or RNA as a cofactor. One of the cleavage sites in PDGF-BB was at the positions 160–162 (R160KK162), which is an important region for receptor binding and activation. In VSMCs, PDGF-BB-stimulated DNA synthesis was inhibited by FSAP in the presence of RNA. RNA was more effective than DNA and the cofactor activity of RNA was neutralized after pretreatment with RNase. FSAP binding to RNA protected the nucleic acid from degradation by RNase. These data are relevant to situations where extracellular nucleic acids released from necrotic or apoptotic cells could activate local FSAP, leading to inhibition of PDGF-BB.
Skip Nav Destination
Article navigation
May 2007
-
Cover Image
Cover Image
- PDF Icon PDF LinkFront Matter
- PDF Icon PDF LinkTable of Contents
- PDF Icon PDF LinkEditorial Board
Research Article|
April 26 2007
Nucleic acids potentiate Factor VII-activating protease (FSAP)-mediated cleavage of platelet-derived growth factor-BB and inhibition of vascular smooth muscle cell proliferation
Aya Shibamiya;
Aya Shibamiya
*Institute for Biochemistry, Medical Faculty, Justus-Liebig-University, 35392 Giessen, Germany
†Graduate School of Health Sciences, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8519, Japan
Search for other works by this author on:
Lars Muhl;
Lars Muhl
*Institute for Biochemistry, Medical Faculty, Justus-Liebig-University, 35392 Giessen, Germany
Search for other works by this author on:
Susanne Tannert-Otto;
Susanne Tannert-Otto
*Institute for Biochemistry, Medical Faculty, Justus-Liebig-University, 35392 Giessen, Germany
Search for other works by this author on:
Klaus T. Preissner;
Klaus T. Preissner
*Institute for Biochemistry, Medical Faculty, Justus-Liebig-University, 35392 Giessen, Germany
Search for other works by this author on:
Sandip M. Kanse
Sandip M. Kanse
1
*Institute for Biochemistry, Medical Faculty, Justus-Liebig-University, 35392 Giessen, Germany
1To whom correspondence should be addressed (email sandip.kanse@biochemie.med.uni-giessen.de).
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
January 31 2007
Accepted:
February 14 2007
Accepted Manuscript online:
February 14 2007
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2007 Biochemical Society
2007
Biochem J (2007) 404 (1): 45–50.
Article history
Received:
January 31 2007
Accepted:
February 14 2007
Accepted Manuscript online:
February 14 2007
Citation
Aya Shibamiya, Lars Muhl, Susanne Tannert-Otto, Klaus T. Preissner, Sandip M. Kanse; Nucleic acids potentiate Factor VII-activating protease (FSAP)-mediated cleavage of platelet-derived growth factor-BB and inhibition of vascular smooth muscle cell proliferation. Biochem J 15 May 2007; 404 (1): 45–50. doi: https://doi.org/10.1042/BJ20070166
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Captcha Validation Error. Please try again.