Heparin stimulates production of bFGF and TGF-beta 1 by human normal, keloid, and fetal dermal fibroblasts.
BACKGROUND
Heparin decreases dermal fibroblast proliferation and collagen production according to several studies. Heparin may mediate these effects by altering the levels of growth factors such as basic fibroblast growth factor (bFGF) and transforming growth factor-beta 1 (TGF-b1). This study sought to delineate the effect of heparin on proliferation and bFGF and TGF-b1 production by human normal, keloid, and fetal dermal fibroblasts.


METHODS
Human normal, keloid, and fetal dermal fibroblasts were propagated in a serum-free in vitro model, with exposure to 0 microg/ml, 50 microg/ml, 300 microg/ml, or 600 microg/ml heparin for 0, 24, 72, or 96 hours. Cell counts were determined by phase contrast microscopy. Levels of bFGF and TGF-b1 in the supernatants were determined by enzyme-linked immunosorbant assay (ELISA).


RESULTS
Heparin inhibited keloid and fetal fibroblast proliferation. All doses of heparin significantly stimulated production of bFGF by normal (341% to 1137% increase), keloid (237% to 1955% increase), and fetal fibroblasts (292% to 1866% increase) at all time points (p<0.05). Heparin (300 microg/ml and 600 microg/ml) also stimulated production of TGF-b1 by normal (56% to 75%), keloid (105% to 269%), and fetal fibroblasts (25% to 57%), with statistical significance (p<0.05) at various time points. 600 microg/ml heparin generally caused the greatest increase in growth factor levels.


CONCLUSIONS
Heparin inhibits proliferation by keloid and fetal fibroblasts and significantly stimulates production of bFGF and TGF-b1 by normal, keloid, and fetal dermal fibroblasts. These effects of heparin on dermal fibroblasts may have implications for wound healing in vivo.
Carroll
Lisa A
LA
Wound Healing and Tissue Engineering Laboratory, Division of Otolaryngology/Head and Neck Surgery, Stanford University Medical Center, Stanford, CA, USA. leacarroll@hotmail.com
Koch
R James
RJ
D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D004305:Dose-Response Relationship, Drug; D005333:Fetus / Q000166:cytology / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis*; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism*; D006493:Heparin / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D007627:Keloid / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D012867:Skin / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*; D053773:Transforming Growth Factor beta1; D014945:Wound Healing / Q000502:physiology
D016895:Culture Media, Serum-Free; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D016222:Fibroblast Growth Factor 2; D006493:Heparin