![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 18, Issue 11, 4543-4552, November 2007
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
,
,
,
*Department of Biochemistry and Molecular Biology, Aging-associated Vascular Disease Research Center, and Department of Pathology, College of Medicine, Yeungnam University, Daegu 705-717, Republic of Korea; and Department of Microbiology, College of Natural Science, Kyungpook National University, Daegu 702-701, Republic of Korea
Submitted March 27, 2007;
Revised August 21, 2007;
Accepted August 29, 2007
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 micro-RNA 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 
-galactosidase (SA--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--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.
Address correspondence to: Jae-Ryong Kim (kimjr{at}ynu.ac.kr).
Abbreviations used: GAPDH, glyceraldehyde-3-phosphate dehydrogenase; HUVEC, human umbilical vein endothelial cell; HDF, human dermal fibroblast; IGF, insulin-like growth factor; IGFBP-5, IGF-binding protein-5; PD, population doublings; SA--gal, senescence-associated -galactosidase.
This article has been cited by other articles:
|
|
 |
|
  R. R. Reddel Senescence: an antiviral defense that is tumor suppressive? Carcinogenesis, January 1, 2010; 31(1): 19 - 26. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Binet, D. Ythier, A. I. Robles, M. Collado, D. Larrieu, C. Fonti, E. Brambilla, C. Brambilla, M. Serrano, C. C. Harris, et al. WNT16B Is a New Marker of Cellular Senescence That Regulates p53 Activity and the Phosphoinositide 3-Kinase/AKT Pathway Cancer Res., December 15, 2009; 69(24): 9183 - 9191. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Yasuoka, E. Hsu, X. D. Ruiz, R. A. Steinman, A. M.K. Choi, and C. A. Feghali-Bostwick The Fibrotic Phenotype Induced by IGFBP-5 Is Regulated by MAPK Activation and Egr-1-Dependent and -Independent Mechanisms Am. J. Pathol., August 1, 2009; 175(2): 605 - 615. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. J. Kim, K. S. Kim, S. H. Kim, S.-H. Baek, H. Y. Kim, C. Lee, and J.-R. Kim Induction of Cellular Senescence by Secretory Phospholipase A2 in Human Dermal Fibroblasts through an ROS-Mediated p53 Pathway J Gerontol A Biol Sci Med Sci, March 4, 2009; (2009) gln055v1. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. J Allan, J. Beattie, and D. J Flint Epithelial injury induces an innate repair mechanism linked to cellular senescence and fibrosis involving IGF-binding protein-5 J. Endocrinol., November 1, 2008; 199(2): 155 - 164. [Abstract] [Full Text] [PDF]
|
|
