Skip Navigation

This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (3)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Nagasaki, T.
Right arrow Articles by Otani, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Nagasaki, T.
Right arrow Articles by Otani, S.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Nephrol Dial Transplant (1999) 14: 1861-1866
© 1999 European Renal Association-European Dialysis and Transplant Association

{alpha}v Integrin regulates TNF-{alpha}-induced nitric oxide synthesis in rat mesangial cells—possible role of osteopontin

Toshiki Nagasaki1, Eiji Ishimura2, Hidenori Koyama2, Atsushi Shioi2, Shuichi Jono2, Masaaki Inaba2, Tadayoshi Hasuma1, Minehiko Yokoyama3, Yoshiki Nishizawa2, Hirotoshi Morii2 and Shuzo Otani1

1 Second Department of Biochemistry and 2 Second Department of Internal Medicine,Osaka City University Medical School, Osaka and 3 Meiji Institute of Health Science,Odawara, Japan

Correspondence and offprint requests to: Eiji Ishimura MD PhD, Second Department of Internal Medicine, Osaka City University MedicalSchool, 1–4-3, Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan.

Background. Tumour necrosis factor-{alpha} (TNF-{alpha}) induces nitric oxide (NO) synthesis in rat mesangial cells (MCs). We previously demonstrated that osteopontin (OP), a matrix protein that mainly interacts with the{alpha}v integrin family, increased time-dependently by TNF-{alpha} stimulation at gene and protein levels. The regulation of NO synthesis by integrins or matrixproteins is unclear.

Methods. We examined whether integrin, especially{alpha}v integrin, regulates NO synthesis in rat MCs and whether OP, an{alpha}v integrin ligand, has an effect on TNF-{alpha}-induced NO synthesis. Furthermore, OP and inducible NO synthase (iNOS) gene expression wasexamined by Northern blotting.

Results. TNF-{alpha} increased NO synthesis in MCs in a time-dependent manner. Synthetic GRGDSP peptide, whichis known to inhibit various integrins that interact with RGD-containing extracellular matrices,increased TNF-{alpha}-induced NO levels in a dose-dependent manner. Cyclical RGD peptide, the specific inhibitor of{alpha}v integrin, also exhibited a dose-dependent effect of increasing NO levels, while GRGESP peptide,which has very low affinity to integrins, had no effect. In addition, NO synthesis was found to besignificantly reduced when MCs were plated on OP-coated dishes compared to type I or IVcollagen-coated dishes. Furthermore, anti-OP antibody increased NO synthesis in MCs. iNOSmRNA levels were increased by TNF-{alpha}, and were abruptly diminished after OP mRNA was significantly induced.

Conclusions. The present study demonstrated the involvement of{alpha}v integrin in TNF-{alpha}-induced NO synthesis in rat MCs, and the possible role of OP was suggested in themechanism. TNF-{alpha} and extracellular matrices can co-operate to regulate the behaviour of MCs at least partlythrough NO synthesis, which may participate in the course of glomerular diseases.

Keywords: {alpha}v integrin; mesangial cell; nitric oxide; osteopontin; tumour necrosis factor-{alpha}


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.