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TGF‐β1 Modulates HGF/SF in Keloid Fibroblast Cell Culture

Ramin Naim, Andreas Naumann, J. A. Barnes, Alexander Walter Sauter, Karl Hörmann, Marc Boris Bloching

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Abstract

Objective Abnormal wound healing processes can result in hypertrophic scars and keloids. TGF‐β1 and HGF/SF are biphasic growth factor cytokines in physiological and pathophysiological conditions. TGF‐β1 has been found to be pivotal in the formation of keloid tissue and therefore neutralising antibodies may allow wound healing without keloid formation. TGF‐β1 has been reported to be antagonised by HGF/SF. Some authors have reported that exogenous administration of HGF/SF prevented scar formation. Hence in this study, we targeted TGF‐β1 and determined the levels of HGF/SF in fibroblast cell culture. Methods Keloid tissue was taken from 7 patients while another 7 patients with mature non‐hypertrophic scar served as controls. All tissues were cultured and fibroblast cultures were used for further experiments. TGF‐β1 antisense was administered at 3 and 6 μmol/ml and HGF/SF levels were determined after 16, 24 and 48 hours of incubation. Results 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 87.66pg/ml after 48 hours of incubation). Conclusions In conclusion, targeting TGF‐β1 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 minimise keloid formation. Nevertheless, wound healing is the result of many interacting cytokines and therefore neutralising or targeting one protein could result in no significant effect.

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Objective Abnormal wound healing processes can result in hypertrophic scars and keloids. TGF‐β1 and HGF/SF are biphasic growth factor cytokines in physiological and pathophysiological conditions. TGF‐β1 has been found to be pivotal in the formation of keloid tissue and therefore neutralising antibodies may allow wound healing without keloid formation. TGF‐β1 has been reported to be antagonised by HGF/SF. Some authors have reported that exogenous administration of HGF/SF prevented scar formation. Hence in this study, we targeted TGF‐β1 and determined the levels of HGF/SF in fibroblast cell culture. Methods Keloid tissue was taken from 7 patients while another 7 patients with mature non‐hypertrophic scar served as controls. All tissues were cultured and fibroblast cultures were used for further experiments. TGF‐β1 antisense was administered at 3 and 6 μmol/ml and HGF/SF levels were determined after 16, 24 and 48 hours of incubation. Results 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 87.66pg/ml after 48 hours of incubation). Conclusions In conclusion, targeting TGF‐β1 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 minimise keloid formation. Nevertheless, wound healing is the result of many interacting cytokines and therefore neutralising or targeting one protein could result in no significant effect.

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Available abstract

Objective Abnormal wound healing processes can result in hypertrophic scars and keloids. TGF‐β1 and HGF/SF are biphasic growth factor cytokines in physiological and pathophysiological conditions. TGF‐β1 has been found to be pivotal in the formation of keloid tissue and therefore neutralising antibodies may allow wound healing without keloid formation. TGF‐β1 has been reported to be antagonised by HGF/SF. Some authors have reported that exogenous administration of HGF/SF prevented scar formation. Hence in this study, we targeted TGF‐β1 and determined the levels of HGF/SF in fibroblast cell culture. Methods Keloid tissue was taken from 7 patients while another 7 patients with mature non‐hypertrophic scar served as controls. All tissues were cultured and fibroblast cultures were used for further experiments. TGF‐β1 antisense was administered at 3 and 6 μmol/ml and HGF/SF levels were determined after 16, 24 and 48 hours of incubation. Results 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 87.66pg/ml after 48 hours of incubation). Conclusions In conclusion, targeting TGF‐β1 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 minimise keloid formation. Nevertheless, wound healing is the result of many interacting cytokines and therefore neutralising or targeting one protein could result in no significant effect.

Key concepts: Keloid, Fibroblast, Hypertrophic scar, Wound healing, Transforming growth factor, Incubation, Scars, Hepatocyte growth factor

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