Adenovirus-mediated transfer of the HST-1 (FGF4) gene induces increased levels of platelet count in vivo.
The HST-1 (fibroblast growth factor 4, FGF4) protein is a potent mitogen for a variety of cell types of mesodermal and neuroectodermal origin, including fibroblasts, endothelial cells, and melanocytes in vitro. To identify the cells and tissue targets of HST-1 in vivo, adenovirus-mediated HST-1 gene transfer was performed. In nude mice, intraperitoneal injection of 3 x 10(9) plaque-forming units of adenoviruses carrying the HST-1 gene (Adex1HST-1L) caused an increase in the number of platelets in the peripheral blood. The number of platelets reached twice the pretreated level by 12 days after the virus injection and the increased level continued up to 20-30 days thereafter. Administration of recombinant HST-1 protein resulted in a transient increase in the platelet count. The number of megakaryocytes in the bone marrow and spleen of the animals with Adex1HST-1L was increased compared with the control animals. Other hematological changes attributed to HST-1 were not observed. Although the mechanisms involved in increased levels of platelet count by HST-1 protein remain to be elucidated, these findings also suggest that adenovirus with the HST-1 gene may be efficiently used for the treatment of thrombocytopenia in various diseases.
Sakamoto
H
H
Genetics Division, National Cancer Center Research Institute, Tokyo, Japan.
Ochiya
T
T
Sato
Y
Y
Tsukamoto
M
M
Konishi
H
H
Saito
I
I
Sugimura
T
T
Terada
M
M
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001792:Blood Platelets / Q000166:cytology*; D001854:Bone Marrow Cells; D002460:Cell Line; D051519:Fibroblast Growth Factor 4; D005346:Fibroblast Growth Factors / Q000008:administration & dosage* / Q000235:genetics; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006410:Hematopoiesis / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008533:Megakaryocytes / Q000166:cytology; D051379:Mice; D008819:Mice, Nude; D010976:Platelet Count; D011518:Proto-Oncogene Proteins / Q000008:administration & dosage* / Q000235:genetics; D013154:Spleen / Q000166:cytology
C496445:FGF4 protein, human; C496446:Fgf4 protein, mouse; D051519:Fibroblast Growth Factor 4; D011518:Proto-Oncogene Proteins; D005346:Fibroblast Growth Factors