Role of insulin-like growth factor binding protein-3 in human umbilical vein endothelial cell senescence.
Whereas insulin-like growth factor binding protein-3 (IGFBP-3) is frequently upregulated in senescent replicatively exhausted human umbilical vein endothelial cells (HUVEC), a systematic analysis of four different HUVEC donors revealed that IGFBP-3 is not consistently upregulated in all isolates at senescence. Lentiviral overexpression of IGFBP-3 inhibited cell proliferation, induced apoptosis and senescence in young HUVEC. Knockdown of IGFBP-3 in senescent HUVEC by lentivirally expressed shRNA did not revert but rather enforced senescence-associated beta-galactosidase staining and apoptosis. Together the data suggest that, although IGFBP-3 acts as an anti-proliferative and premature senescence-inducing protein, the role of IGFBP-3 on senescence depends on the genetic background of the donor, and additional factors might be important to maintain the senescent phenotype.
Muck
Christoph
C
Institute for Biomedical Aging Research, Austrian Academy of Sciences, Innsbruck, Austria.
Micutkova
Lucia
L
Zwerschke
Werner
W
Jansen-Durr
Pidder
P
D015153:Blotting, Western; D049109:Cell Proliferation; D016922:Cellular Senescence; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism*; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism*; D014161:Transduction, Genetic; D014471:Umbilical Veins / Q000166:cytology* / Q000378:metabolism*
D018972:Insulin-Like Growth Factor Binding Protein 3