title: The role of fructose-1,6-diphosphate in cell migration and proliferation in an in vitro xenograft blood vessel model of vascular wound healing.
abstract: Both smooth muscle cells and endothelial cells play an important role in vascular wound healing. To elucidate the role of fructose-1,6-diphosphate, cell proliferation and cell migration studies were performed with human endothelial cells and rat smooth muscle cells. To mimic blood vessels, endothelial and smooth muscle cells were used in 1:10, 1:5, and 1:1 concentrations, respectively, mimicking large-, mid-, and capillary-sized blood vessels. Cell migration was studied with fetal bovine serum-starved cells. For cell proliferation assay, cells were plated at 30-50% confluency and then starved. The cells were incubated for 48 h with fructose-1,6-diphosphate at (per ml) 10 mg, 1 mg, 500 microg, 250 microg, 100 microg, and 10 microg, pulsed with tritiated-thymidine and incubated with 1 N NaOH for 30 min at room temperature, harvested, and counted. For migration assay, confluent cells were starved, wounded, and incubated for 24 h with same concentrations of fructose-1,6-diphosphate as in proliferation assay. The cells were fixed and counted. Smooth muscle cell proliferation was inhibited by fructose-1,6-diphosphate at 10 mg/ml. In the xenograft models of 1:10, 1:5, and 1:1 fructose-1,6-diphosphate inhibited proliferation at 10 mg/ml. In migration studies 10 mg fructose-1,6-diphosphate per ml was inhibitory to both cell types. In large-, mid-, and capillary-sized blood vessels, fructose-1,6-diphosphate inhibited proliferation of both cell types at 10 mg/ml. At the individual cell level, fructose-1,6-diphosphate is nonstimulatory to proliferation of endothelial cells while inhibiting migration, and it acts on smooth muscle cells by inhibiting both proliferation and migration.
authors.affiliation: Department of Surgery, University of Mississippi Medical Center, Jackson 39216-4505, USA.
authors.forename: H H
authors.initials: HH
authors.lastname: Cohly
authors.forename: J W
authors.initials: JW
authors.lastname: Stephens
authors.forename: M F
authors.initials: MF
authors.lastname: Angel
authors.forename: J C
authors.initials: JC
authors.lastname: Johnson
authors.forename: A K
authors.initials: AK
authors.lastname: Markov
mesh_terms: D000818:Animals; D001011:Aorta / Q000166:cytology; D002417:Cattle; D002455:Cell Division / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D018920:Coculture Techniques; D016895:Culture Media, Serum-Free; D004730:Endothelium, Vascular / Q000166:cytology*; D005635:Fructosediphosphates / Q000378:metabolism*; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014183:Transplantation, Heterologous; D014680:Veins / Q000166:cytology; D014945:Wound Healing / Q000502:physiology*
chemical_list: D016895:Culture Media, Serum-Free; D005635:Fructosediphosphates; C029063:fructose-1,6-diphosphate