Skip Navigation



Journal of Biochemistry Advance Access published online on July 7, 2006
Journal of Biochemistry, doi:10.1093/jb/mvj146
This Article
Right arrow Advance Access manuscript (PDF)
Right arrow All Versions of this Article:
140/2/193    most recent
mvj146v1
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 Tatano, Y.
Right arrow Articles by Itoh, K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Tatano, Y.
Right arrow Articles by Itoh, K.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 2006 The Japanese Biochemical Society.
Received February 20, 2006
Accepted May 21, 2006

Regular Paper

Significant Decrease in Tropoelastin Gene Expression in Fibroblasts from a Japanese Costello Syndrome Patient with Impaired Elastogenesis and Enhanced Proliferation

Yutaka Tatano 1, Tsutomu Takahashi 2, Daisuke Tsuji 1, Naohiro Takeuchi 3, Kohji Tsuta 3, Goro Takada 2, Mai Ohsawa 4, Hitoshi Sakuraba 4, and Kohji Itoh 1 *

1 Department of Medicinal Biotechnology, Institute for Medicinal Resources, Graduate School of Pharmaceutical Sciences, The University of Tokushima, Tokushima 770-8505, Japan; CREST, JST, Saitama 332-0012, Japan
2 Department of Pediatrics, Akita University of Medical School, Akita 010-8543, Japan
3 Department of Medicinal Biotechnology, Institute for Medicinal Resources, Graduate School of Pharmaceutical Sciences, The University of Tokushima, Tokushima 770-8505, Japan
4 Department of Clinical Genetics, The Tokyo Metropolitan Institute of Medical Science, Tokyo Metropolitan Organization for Medical Research, Tokyo 113-8613, Japan; CREST, JST, Saitama 332-0012, Japan

* To whom correspondence should be addressed.
Kohji Itoh, E-mail: kitoh{at}ph.tokushima-u.ac.jp


  Abstract

Costello syndrome is a connective tissue disorder associated with sparse, thin, and fragmented elastic fibers in tissues. In this study we demonstrated a significant decrease in the expression of tropoelastin mRNA in fibroblasts derived from a Japanese Costello syndrome patient with impaired elastogenesis and enhanced proliferation. In contrast, there were no changes in expression of the Harvey ras (HRAS), fibrillin-1, fibulin-5, microfibril-associated glycoprotein-1 (MAGP-1), lysyl oxidase (LOX), or 67-kDa non-integrin elastin-binding protein (EBP) gene. The proliferative activity of the Costello fibroblasts was about 4-fold higher than that of the normal and pathological control ones. However, no mutations were detected in the coding region of HRAS mRNA. Transduction of the bovine tropoelastin (bTE) gene with the lentiviral vector restored the elastic fiber formation and decreased the growth rate in the Costello fibroblasts. These results strongly suggest that the defect of human tropoelastin (hTE) gene expression should induce the impaired elastogenesis and enhanced proliferation of Costello fibroblasts, and that a primary cause other than the HRAS gene mutation should contribute to the pathogenesis in the present Costello case.

Keywords: Costello syndrome; Elastogenesis; Lentiviral vector; Proliferation; Tropoelastin.
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.