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

2007 ◽  
Vol 18 (11) ◽  
pp. 4543-4552 ◽  
Author(s):  
Kwang Seok Kim ◽  
Young Bae Seu ◽  
Suk-Hwan Baek ◽  
Mi Jin Kim ◽  
Keuk Jun Kim ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Endothelial Cells ◽  
Growth Factor ◽  
Cellular Senescence ◽  
Vascular Diseases ◽  
Dermal Fibroblasts ◽  
Micro Rna ◽  
Positive Staining ◽  
Insulin Like Growth Factor ◽  
Igf Binding Proteins

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 β-galactosidase (SA-β-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-β-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.

Effects of Maternal Diabetes on Fetal Expression of Insulin-Like Growth Factor and Insulin-Like Growth Factor Binding Protein MRNAs in the Rat

1995 ◽  
Vol 147 (2) ◽  
pp. R5-R8 ◽  
Author(s):  
Randal D. Streck ◽  
Veeraramani S. Rajaratnam ◽  
Renata B. Fishman ◽  
Peggy J. Webb
Keyword(s):  
Growth Factor ◽  
Mrna Expression ◽  
Fetal Growth ◽  
Fetal Liver ◽  
Expression Patterns ◽  
Maternal Diabetes ◽  
Limb Bud ◽  
Insulin Like Growth Factor ◽  
Igf Binding Proteins ◽  
Increased Risk

ABSTRACT Matemal diabetes is associated in humans and rats with an increased risk for fetal growth abnormalities and malformations. Therefore, the effect of maternal diabetes on expression of genes that regulate fetal growth and differentiation is of considerable interest. Developmental growth is regulated in part by the expression and availability of insulin-like growth factors (IGFs). Postnatal expression of a subset of the IGFs and IGF binding proteins (IGFBPs) has been demonstrated to be regulated in response to diabetes and other metabolic conditions. We used in situ hybridization to analyze the effect of maternal diabetes, induced by streptozotocin (STZ) prior to mating, upon prenatal rat IGF and IGFBP mRNA expression. At gestational day (GD) 14, the most striking effect of maternal diabetes on fetal IGF/IGFBP gene expression was a marked increase in the abundance of IGFBP-1 mRNA within the liver primordia of fetuses isolated from diabetic dams compared to age-matched controls. This upregulation cannot be entirely due to the approximately one-half-day delay in fetal development (based on limb bud staging) associated with maternal diabetes, as there was no gross difference in the level of IGFBP-1 mRNA between GD13 and GD14 control fetal livers. In contrast, the fetal mRNA expression patterns of IGF-I, IGF-II and IGFBP-2, -3, -4, -5 and -6 were not grossly altered by maternal diabetes. These data are consistent with the hypothesis that IGFBP-1 produced within the fetal liver and secreted into fetal circulation may play a role in regulating rat fetal growth.

Ethanol-Induced Inhibition of Cell Proliferation Is Modulated by Insulin-Like Growth Factor-I Receptor Levels

1996 ◽  
Vol 20 (5) ◽  
pp. 961-966 ◽  
Author(s):  
Mariana Resnicoff ◽  
Shijun Cui ◽  
Domenico Coppola ◽  
Jan B. Hoek ◽  
Raphael Rubin
Keyword(s):  
Cell Proliferation ◽  
Growth Factor ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Growth Factor I

Insulin-like growth factor (IGF)-binding proteins: interactions with IGFs and intrinsic bioactivities

2000 ◽  
Vol 278 (6) ◽  
pp. E967-E976 ◽  
Author(s):  
Robert C. Baxter
Keyword(s):  
Growth Factor ◽  
Binding Proteins ◽  
Specific Cell ◽  
Type I ◽  
Insulin Like Growth Factor ◽  
Serine Kinase ◽  
Homologous Proteins ◽  
Igf Binding Proteins ◽  
Type I Igf Receptor ◽  
Igf Binding

The insulin-like growth factor (IGF)-binding proteins (IGFBPs) are a family of six homologous proteins with high binding affinity for IGF-I and IGF-II. Information from NMR and mutagenesis studies is advancing knowledge of the key residues involved in these interactions. IGF binding may be modulated by IGFBP modifications, such as phosphorylation and proteolysis, and by cell or matrix association of the IGFBPs. All six IGFBPs have been shown to inhibit IGF action, but stimulatory effects have also been established for IGFBP-1, -3, and -5. These generally involve a decrease in IGFBP affinity and may require cell association of the IGFBP, but precise mechanisms are unknown. The same three IGFBPs have well established effects that are independent of type I IGF receptor signaling. IGFBP-1 exerts these effects by signaling through α5β1-integrin, whereas IGFBP-3 and -5 may have specific cell-surface receptors with serine kinase activity. The regulation of cell sensitivity to inhibitory IGFBP signaling may play a role in the growth control of malignant cells.

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