Autocrine control of wound repair by insulin-like growth factor I in cultured endothelial cells.
The repair process of the vascular endothelium is modulated by growth factors from both endogenous (within the vessel wall) and exogenous (blood borne) sources. We utilized a tissue culture model of endothelial wounding to gain further insight into the potential autocrine control of proliferation during wound repair. Cultured porcine aortic endothelial monolayers were mechanically wounded by passing a 7-mm sterile glass rod over the surface of the culture. Proliferation at the wound edge was quantified using [3H]thymidine autoradiography. In wounded cultures incubated in media supplemented with 10% fetal calf serum, 81 +/- 2% of the nuclei at the wound edge were labeled. When the cultures were incubated in serum-free media, proliferation at the wound edge was only slightly diminished with 65 +/- 3% (P < 0.05) of the cells labeled. These findings raise the possibility that there is a significant contribution from autocrine growth factors to endothelial wound repair. To evaluate the potential role of insulin-like growth factor I (IGF-I) in the wound repair process, we used a radioimmunoassay to measure IGF-I secretion. Wounded cultures exhibited a 187 +/- 58% increase in IGF-I production when compared with nonwounded cultures (P < 0.05). To determine the extent to which endogenous IGF-I mediates the proliferative response of endothelial cell monolayers to wounding, wounded cultures were incubated with inactivating concentrations of IGF-I antibody. When IGF-I antibody was present in the culture media, only 26 +/- 3% of the nuclei at the wound edge were labeled with [3H]thymidine (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Taylor
W R
WR
Department of Medicine, Emory University, Atlanta 30322.
Alexander
R W
RW
D000818:Animals; D002455:Cell Division; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000293:injuries* / Q000503:physiopathology*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000502:physiology*; D014945:Wound Healing / Q000502:physiology*
D007334:Insulin-Like Growth Factor I