The Journal of Experimental Medicine
Torrey Pines Biolabs
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published online December 24, 2007
doi:10.1084/jem.20071324
The Journal of Experimental Medicine, Vol. 205, No. 1, 25-33
The Rockefeller University Press, 0022-1007 $30.00
© 2007 Kon et al.
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 2826K)
Right arrow PPT slides of all figures
Right arrow Supplemental Material Index
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JEM
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kon, S.
Right arrow Articles by Uede, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kon, S.
Right arrow Articles by Uede, T.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

BRIEF DEFINITIVE REPORT

 Syndecan-4 protects against osteopontin-mediated acute hepatic injury by masking functional domains of osteopontin

Shigeyuki Kon1, Masahiro Ikesue1, Chiemi Kimura1, Momoe Aoki1, Yosuke Nakayama1, Yoshinari Saito1, Daisuke Kurotaki1, Hongyan Diao1, Yutaka Matsui2, Tatsuya Segawa3, Masahiro Maeda3, Tetsuhito Kojima4, and Toshimitsu Uede1

1 Division of Molecular Immunology and 2 Department of Matrix Medicine, Institute for Genetic Medicine, Hokkaido University, Kita-ku, Sapporo 060-0815, Japan
3 Immuno-Biological Laboratories Co., Ltd., Takasaki 370-0831, Japan
4 Department of Medical Technology, Nagoya University School of Health Sciences, Higashi-ku, Nagoya 461-8673, Japan

CORRESPONDENCE Toshimitsu Uede: toshi{at}igm.hokudai.ac.jp

Osteopontin (OPN) is a T helper type 1 immunoregulatory cytokine that plays a critical role in various inflammatory disorders. OPN exerts proinflammatory reactions through interaction with integrin receptors. OPN function can be modulated by protease digestion. However, the molecular mechanisms that regulate OPN function in vivo have not been elucidated. There are two putative heparin-binding domains (HBDs) within the OPN molecule, which may bind both heparin and heparin-like glycosaminoglycans such as syndecan. We show that expression of OPN and syndecan-4 is significantly up-regulated after concanavalin-A (ConA) injection. Syndecan-4 binds to one of the HBDs of OPN, which overlaps with the thrombin cleavage site of OPN. When OPN is associated with syndecan-4, syndecan-4 masks both the thrombin cleavage and the integrin binding sites within OPN. Importantly, syndecan-4–deficient (Syn4KO) mice are more susceptible to hepatic injury, and the thrombin-cleaved form of OPN is significantly elevated in Syn4KO mice as compared with wild-type mice after ConA injection. Finally, we demonstrate that administration of purified syndecan-4 protects mice from ConA-induced hepatic injury. Thus, syndecan-4 is a critical intrinsic regulator of inflammatory reactions via its effects on OPN function and is a potential novel therapeutic tool for treating inflammatory diseases.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search
TABLE OF CONTENTS