Efficient transfer of genes into senescent cells by adenovirus vectors via highly expressed alpha v beta 5 integrin.
Although various methods for transferring genes into mammalian cells have been established, none have been successful with senescent cells. In this report, we present evidence of the efficient transfer of a gene into human senescent fibroblasts using an adenoviral vector. By employing a recombinant adenovirus vector harboring the beta-galactosidase gene (Ad-CAG beta NR), we observed a good correlation between the proportion of beta-galactosidase positive cells and population doubling of the infected cells. In addition, 1.5- to 6.0-fold greater beta-galactosidase activity was observed in senescent fibroblasts (population doubling [PD] = 58) than in young cells (PD = 15). Western blotting analysis revealed that, compared with young fibroblasts, senescent fibroblasts expressed larger amounts of alpha v beta 5 and alpha v beta 3 integrins which were thought to form part of the adenovirus receptor. These results suggest that higher expression of alpha v beta 5 and alpha v beta 3 integrins in senescent cells renders them more sensitive to adenovirus infection than young cells. Thus, adenovirus vectors may prove to be useful in gene therapy strategies directed against senescence-related disorders.
Hashimoto
Y
Y
Department of Urology, Nagoya City University, Japan.
Kohri
K
K
Akita
H
H
Mitani
K
K
Ikeda
K
K
Nakanishi
M
M
D000256:Adenoviridae / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D002460:Cell Line; D048429:Cell Size; D016922:Cellular Senescence / Q000235:genetics; D005347:Fibroblasts; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D016023:Integrins / Q000096:biosynthesis* / Q000235:genetics*; D011991:Receptors, Virus / Q000378:metabolism; D019030:Receptors, Vitronectin
D016023:Integrins; D011991:Receptors, Virus; D019030:Receptors, Vitronectin; C064660:integrin alphaVbeta5