Proliferative capacity of venous ulcer wound fibroblasts in the presence of platelet-derived growth factor.
Growth factors have been demonstrated to increase the proliferation of wound fibroblasts. Platelet-derived growth factor (PDGF) is a potent cell mitogen. However, the role of PDGF in chronic venous ulcers is inconclusive. This study investigated whether PDGF stimulates venous ulcer fibroblasts to proliferate. Fibroblasts (fb) were isolated from 8 venous ulcers wounds (w-fb) and normal skin (n-fb) of the ipsilateral thigh via punch biopsies. Fibroblasts were plated at 1,500 cells/dish in Dulbecco's Modified Eagle Medium + 10% calf serum (CM) and treated with/without PDGF-alphabeta (10 ng/mL) for 15 days. Growth rates were calculated. Western blotting and immunocytochemistry staining determined basal levels for PDGF-alpha and -beta receptors, respectively. Growth rates were significantly lower in w-fb than in n-fb (1,579 +/-546 vs 13,782 +/-5,882 cells/day, p=0.019). PDGF-alphabeta treatment caused n-fb to increase their proliferative capacity relative to complete media (20,393 +/-6,572 vs 13,782 +/-5,882 cells/day, p=0.005). However, PDGF-alphabeta had no significant effect on w-fb proliferation over CM (1,030 +/-264 and 1,579 +/-546 cells/day, p=0.15). In the presence of PDGF-alphabeta, w-fb had a significantly attenuated growth rate over n-fb (1,030 +/-264 vs 20,393 +/-6,572 cells/day, p=0.019). Western blot and immunocytochemistry analysis revealed diminished basal levels of PDGF-alpha and -beta receptors, respectively, in ulcer fibroblasts. Venous ulcer fibroblasts had decreased proliferation. PDGF-alphabeta had no effect on the growth rate of venous ulcer fibroblasts. In venous ulcers, decreased basal levels of fibroblast PDGF-alpha and -beta receptors may explain reduced proliferation. Further clinical studies are needed to elucidate the role growth factors may play in venous ulcers.
Department of Surgery, Section of Vascular Surgery, Boston University Medical Center, Boston, MA 02118, USA.
Ricardo
R
Vasquez
Brian J
BJ
Marien
Christopher
C
Gram
David G
DG
Goodwin
James O
JO
Menzoian
Joseph D
JD
Raffetto
D002455:Cell Division / Q000187:drug effects*; D002478:Cells, Cultured; D002908:Chronic Disease; D005347:Fibroblasts / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D017978:Receptors, Growth Factor / Q000187:drug effects; D014647:Varicose Ulcer / Q000503:physiopathology*; D014945:Wound Healing / Q000502:physiology*
D010982:Platelet-Derived Growth Factor; D017978:Receptors, Growth Factor