Molecular Biology of the Cell Sign up for new MBC in Press e-TOCs!

Home Help [Feedback] [For Subscribers] [Archive] [Search] --
QUICK SEARCH:   [advanced]


     

MBC in Press, published online ahead of print September 5, 2007
Mol. Biol. Cell 10.1091/mbc.E07-03-0280

A more recent version of this article appeared on November 1, 2007
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
E07-03-0280v1
18/11/4543    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
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 Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Seok Kim, K.
Right arrow Articles by Kim, J.-R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Seok Kim, K.
Right arrow Articles by Kim, J.-R.

Submitted on March 27, 2007
Revised on August 21, 2007
Accepted on August 29, 2007

Induction of Cellular Senescence by Insulin-like Growth Factor Binding Protein-5 through a p53-dependent Mechanism

Kwang Seok Kim,*{dagger}{ddagger} Young Bae Seu,{ddagger} Suk-Hwan Baek,*{dagger} Mi Jin Kim,{dagger}{sect} Keuk Jun Kim,{dagger}{sect} Jung Hye Kim,* and Jae-Ryong Kim*{dagger}

*Department of Biochemistry and Molecular Biology, {dagger}Aging-associated Vascular Disease Research Center, and {sect}Department of Pathology, College of Medicine, Yeungnam University, Daegu 705-717, Republic of Korea; {ddagger}Department of Microbiology, College of Natural Science, Kyungpook National University, Daegu 702-701, Republic of Korea

Monitoring Editor: Carl-Henrik Heldin

The insulin-like growth factor (IGF) signaling pathway plays a crucial role in the regulation of cell growth, differentiation, apoptosis and aging. IGF binding proteins (IGFBPs) are important members of the IGF axis. IGFBP-5 is up-regulated during cellular senescence in human dermal fibroblasts and endothelial cells, but the function of IGFBP-5 in cellular senescence is unknown. Here we show that IGFBP-5 plays important roles in the regulation of cellular senescence. Knockdown of IGFBP-5 in old human umbilical endothelial cells (HUVECs) with IGFBP-5 microRNA lentivirus caused partial reduction of a variety of senescent phenotypes, such as changes in cell morphology, increases in cell proliferation and decreases in senescence-associated {beta}-galactosidase (SA-{beta}-gal) staining. In addition, treatment with IGFBP-5 protein or up-regulation of IGFBP-5 in young cells accelerates cellular senescence, as confirmed by cell proliferation and SA-{beta}-gal staining. Premature senescence induced by IGFBP-5 up-regulation in young cells was rescued by knockdown of p53, but not by knockdown of p16. Furthermore, atherosclerotic arteries exhibited strong IGFBP-5-positive staining along intimal plaques. These results suggest that IGFBP-5 plays a role in the regulation of cellular senescence via a p53-dependent pathway and in aging-associated vascular diseases. Keywords: cell aging, IGFBP-5, p53, endothelial cells, atherosclerosis

Address correspondence to: Jae-Ryong Kim (kimjr{at}ynu.ac.kr)






Home Help [Feedback] [For Subscribers] [Archive] [Search] --
Copyright © 2007 by The American Society for Cell Biology. Terms of copyright protection, warranties, and disclaimers.