Transforming growth factor-beta1-antisense modulates the expression of hepatocyte growth factor/scatter factor in keloid fibroblast cell culture.

Abnormal wound healing processes can result in hypertrophic scars and keloids. Transforming growth factor-beta1 (TGF-beta1) and hepatocyte growth factor/scatter factor (HGF/SF) are biphasic growth factor cytokines in physiologic and pathophysiologic conditions. Findings have shown TGF-beta1 to be pivotal in the formation of keloid tissue. Therefore, neutralizing antibodies may allow wound healing without keloid formation. As reported, TGF-beta1 is antagonized by HGF/SF. Some authors have reported that exogenous administration of HGF/SF prevented scar formation. Hence, this study targeted TGF-beta1 and determined the levels of HGF/SF in fibroblast cell culture. Keloid tissue was taken from seven patients. Another seven patients with mature nonhypertrophic scar served as controls. All tissues were cultured, and fibroblast cultures were used for further experiments. The TGF-beta1 antisense was administered at 3 and 6 micromol/ml, and HGF/SF levels were determined after 16, 24, and 48 h of incubation. The levels of HGF/SF showed significant differences after incubation with antisense oligonucleotides. The increasing antisense levels resulted in increased HGF/SF levels (up to 87.66 pg/ml after 48 h of incubation). In conclusion, targeting TGF-beta1 resulted in significantly increased levels of HGF/SF. The clinical relevance could include the use of locally administered HGF/SF in protein or gene form to minimize formation of keloids. Nevertheless, wound healing is the result of many interacting cytokines, so neutralizing or targeting one protein could result in no significant effect.