The binding of advanced glycation end-products (AGE) to the receptor for AGE (RAGE) is known to deteriorate various cell functions and is implicated in the pathogenesis of diabetic vascular complications. In the present study, we show that the cellular constituents of small vessels, endothelial cells (EC) and pericytes express novel splice variants of RAGE mRNA coding for the isoforms that lack the N-terminal V-type immunoglobulin-like domain (N-truncated) or the C-terminal transmembrane domain (C-truncated), as well as the known full-length mRNA. The ratio of the expression of the three variants was different between EC and pericytes; the content of the C-truncated form was highest in EC, whereas the full-length form was the most abundant in pericytes. Transfection experiments with COS-7 cells demonstrated that those variant mRNAs were translated into proteins as deduced; C-truncated RAGE was efficiently secreted into the culture media, and N-truncated RAGE was located mainly on the plasma membrane. The three isoforms were also detected in primary cultured human EC and pericytes. Further, full-length and C-truncated forms of RAGE bound to an AGE-conjugated column, whereas N-truncated RAGE did not. The AGE induction of extracellular-signal-related kinase phosphorylation and vascular endothelial growth factor in EC and of the growth and cord-like structure formation of EC was abolished completely by C-truncated RAGE, indicating that this endogenous secretory receptor (endogenous secretory RAGE) is cytoprotective against AGE. The results may contribute to our understanding of the molecular basis for the diversity of cellular responses to AGE and for individual variations in the susceptibility to diabetic vascular complications.
Skip Nav Destination
Follow us on Twitter @Biochem_Journal
Article navigation
March 2003
- PDF Icon PDF LinkFront Matter
Research Article|
March 15 2003
Novel splice variants of the receptor for advanced glycation end-products expressed in human vascular endothelial cells and pericytes, and their putative roles in diabetes-induced vascular injury
Hideto YONEKURA;
Hideto YONEKURA
∗Department of Biochemistry and Molecular Vascular Biology, Kanazawa University Graduate School of Medical Science, Kanazawa 920-8640, Japan
Search for other works by this author on:
Yasuhiko YAMAMOTO;
Yasuhiko YAMAMOTO
∗Department of Biochemistry and Molecular Vascular Biology, Kanazawa University Graduate School of Medical Science, Kanazawa 920-8640, Japan
Search for other works by this author on:
Shigeru SAKURAI;
Shigeru SAKURAI
∗Department of Biochemistry and Molecular Vascular Biology, Kanazawa University Graduate School of Medical Science, Kanazawa 920-8640, Japan
Search for other works by this author on:
Ralica G. PETROVA;
Ralica G. PETROVA
∗Department of Biochemistry and Molecular Vascular Biology, Kanazawa University Graduate School of Medical Science, Kanazawa 920-8640, Japan
Search for other works by this author on:
Md. Joynal ABEDIN;
Md. Joynal ABEDIN
∗Department of Biochemistry and Molecular Vascular Biology, Kanazawa University Graduate School of Medical Science, Kanazawa 920-8640, Japan
Search for other works by this author on:
Hui LI;
Hui LI
∗Department of Biochemistry and Molecular Vascular Biology, Kanazawa University Graduate School of Medical Science, Kanazawa 920-8640, Japan
Search for other works by this author on:
Kiyoshi YASUI;
Kiyoshi YASUI
∗Department of Biochemistry and Molecular Vascular Biology, Kanazawa University Graduate School of Medical Science, Kanazawa 920-8640, Japan
Search for other works by this author on:
Masayoshi TAKEUCHI;
Masayoshi TAKEUCHI
†Department of Biochemistry, Faculty of Pharmaceutical Science, Hokuriku University, Kanazawa 920-1181, Japan
Search for other works by this author on:
Zenji MAKITA;
Zenji MAKITA
‡Division of Endocrinology and Metabolism, Department of Medicine, Kurume University School of Medicine, Kurume 830-0011, Japan,
Search for other works by this author on:
Shin TAKASAWA;
Shin TAKASAWA
§Department of Biochemistry, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan
Search for other works by this author on:
Hiroshi OKAMOTO;
Hiroshi OKAMOTO
§Department of Biochemistry, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan
Search for other works by this author on:
Takuo WATANABE;
Takuo WATANABE
∗Department of Biochemistry and Molecular Vascular Biology, Kanazawa University Graduate School of Medical Science, Kanazawa 920-8640, Japan
Search for other works by this author on:
Hiroshi YAMAMOTO
Hiroshi YAMAMOTO
1
∗Department of Biochemistry and Molecular Vascular Biology, Kanazawa University Graduate School of Medical Science, Kanazawa 920-8640, Japan
1To whom correspondence should be addressed (e-mail [email protected]).
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
September 02 2002
Revision Received:
December 16 2002
Accepted:
December 20 2002
Accepted Manuscript online:
March 15 2003
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London ©2003
2003
Biochem J (2003) 370 (3): 1097–1109.
Article history
Received:
September 02 2002
Revision Received:
December 16 2002
Accepted:
December 20 2002
Accepted Manuscript online:
March 15 2003
Citation
Hideto YONEKURA, Yasuhiko YAMAMOTO, Shigeru SAKURAI, Ralica G. PETROVA, Md. Joynal ABEDIN, Hui LI, Kiyoshi YASUI, Masayoshi TAKEUCHI, Zenji MAKITA, Shin TAKASAWA, Hiroshi OKAMOTO, Takuo WATANABE, Hiroshi YAMAMOTO; Novel splice variants of the receptor for advanced glycation end-products expressed in human vascular endothelial cells and pericytes, and their putative roles in diabetes-induced vascular injury. Biochem J 15 March 2003; 370 (3): 1097–1109. doi: https://doi.org/10.1042/bj20021371
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.
Could not validate captcha. Please try again.
Biochemical Society Member Sign in
Sign InSign in via your Institution
Sign in via your InstitutionGet Access To This Article
Follow us on Twitter @Biochem_Journal
Open Access for all
We offer compliant routes for all authors from 2025. With library support, there will be no author nor reader charges in 5 journals. Check here |
![]() View past webinars > |