Skip Navigation


Journal of Biochemistry Advance Access originally published online on September 6, 2008
Journal of Biochemistry 2008 144(5):571-580; doi:10.1093/jb/mvn106
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplementary Data
Right arrow All Versions of this Article:
144/5/571    most recent
mvn106v1
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 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 Request Permissions
Google Scholar
Right arrow Articles by Wu, G. D.
Right arrow Articles by Klein, A. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wu, G. D.
Right arrow Articles by Klein, A. S.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 2008 The Japanese Biochemical Society

Genetic Modulation of CD44 Expression by Intragraft Fibroblasts

Gordon D. Wu1,*, Hong Wang1, Hui Zhu1, Yao He1, Mark L. Barr2 and Andrew S. Klein1

1Department of Surgery, Comprehensive Transplant Center, Cedars-Sinai Medical Center; and 2Department of Cardiothoracic Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

*To whom correspondence should be addressed. Tel: +1-310-423-5393, Fax: +1-310-423-0565, E-mail: gordon.wu{at}cshs.org

Received March 11, 2008; Accepted August 11, 2008


  Abstract

This study investigated the genetic composition and the functional implication of CD44 species expressed by intragraft fibroblasts. An LEW-to-F344 heart transplant model of chronic rejection was used. Intragraft fibroblasts recovered from the chronically rejecting allografts displayed a 4.5-fold increase in expression of CD44 mRNA when compared with that of the fibroblasts isolated from non-rejecting heart allografts (P < 0.01). The intragraft fibroblasts preferentially expressed CD44 variant isoforms containing v1 exon transcript. Automated nucleotide sequence analysis revealed that the majority (90.12%) of the CD44 v1 isoforms expressed by the rejecting graft fibroblasts were encoded by a mutated CD44 mRNA, which contained two point mutations and a codon deletion in the v1 coding region. Histochemistry demonstrated a massive deposition of extracellular HA in the rejecting heart allografts. Hyaluronic acid (HA) was able to promote in vitro fibroblast adhesion, migration in a CD44-dependent manner, and survival in a serum-free culture condition. The study concludes that up-regulation of CD44 v1 isoforms expressed by the intragraft fibroblasts is associated with an increase in the deposition of extracellular HA, the principal ligand for CD44, in the allografts, suggesting that CD44–HA interaction plays an important role in regulating fibroblast recruitment and growth in allografts developing chronic rejection.

Key Words: CD44, gene expression, HA, intragraft fibroblast, rat

Abbreviations: ECM, extracellular matrix; HA, hyaluronic acid; NG, non-rejecting graft; NH, native heart; RG, rejecting graft


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.