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.
Vasquez
Ricardo
R
Department of Surgery, Section of Vascular Surgery, Boston University Medical Center, Boston, MA 02118, USA.
Marien
Brian J
BJ
Gram
Christopher
C
Goodwin
David G
DG
Menzoian
James O
JO
Raffetto
Joseph D
JD
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