Tgf-beta antisense therapy increases angiogenic potential in human keratinocytes in vitro.

Transforming growth factor-beta (TGF-beta) has been identified as an important component of wound healing. Recent developments in molecular therapy offer exciting prospects for the modulation of wound healing, specifically those targeting TGF-beta. The purpose of this study was to analyze the effect of TGF-beta targeting on the expression of angiogenic vascular endothelial growth factor (VEGF), a key regulator of angiogenesis, and in vitro angiogenic activity. Expression of angiogenic VEGF in tissue samples from chronic dermal wounds was investigated by immunohistochemistry. The effect of TGF-beta targeting using antisense oligonucleotides on the expression of VEGF was analyzed by ELISA and RT-PCR in cultured human keratinocytes. Human endothelial cells (EC) were grown in conditioned medium produced from the treated keratinocytes. EC migration was measured using a modified Boyden chamber, EC tube formation was analyzed under the light microscope. Immunohistochemical investigation demonstrated a decreased expression of VEGF protein in tissue samples from chronic dermal wounds compared to normal human skin. Antisense TGF-beta oligonucleotide treatment upregulated VEGF secretion in vitro. Addition of conditioned medium from TGF-beta antisense-treated keratinocytes resulted in an increase of endothelial cell migration and tube formation. Our results demonstrate that TGF-beta antisense oligonucleotide technology may be a potential therapeutic option for stimulation of angiogenesis in chronic wounds.

Riedel K ，Riedel F ，Goessler UR ，Germann G ，Sauerbier M ... -  《ARCHIVES OF MEDICAL RESEARCH》

Abrogation of TGF-beta by antisense oligonucleotides modulates expression of VEGF and increases angiogenic potential in isolated fibroblasts from radiated skin.

The transforming growth factor-beta (TGF-beta) has been identified as an important component of wound healing. Recent developments in molecular therapy offer good prospects for the modulation of wound healing, specifically those targeting TGF-beta. The aim of this study was to analyze the effect of TGF-beta targeting on the expression of angiogenic vascular endothelial growth factor (VEGF), a key regulator of angiogenesis and in vitro angiogenic activity in fibroblasts isolated from radiation-induced chronic dermal wounds. The expression of angiogenic VEGF in tissue samples from radiation-induced chronic dermal wounds was investigated by immunohistochemistry and microarray technique. The effect of TGF-beta targeting using antisense oligonucleotides on the expression of VEGF in isolated fibroblasts was analyzed by ELISA and multiplex RT-PCR. Human endothelial cells (ECs) were grown in conditioned medium produced from the treated fibroblasts. EC migration was measured using a modified Boyden chamber; EC tube formation was analyzed under a light microscope. Immunohistochemical investigation and microarray analysis demonstrated a decreased expression of VEGF protein and mRNA in tissue samples from radiation-induced chronic dermal wounds compared to normal human skin. Antisense TGF-beta oligonucleotide treatment significantly up-regulated VEGF secretion in vitro. Addition of conditioned medium from TGF-beta antisense-treated fibroblasts resulted in an increase in EC cell migration and tube formation. In conclusion, our results demonstrate that TGF-beta antisense oligonucleotide technology may be a potential therapeutic option for stimulation of angiogenesis in radiation-induced dermal wounds.

Riedel K ，Koellensperger E ，Ryssel H ，Riedel F ，Goessler UR ，Germann G ，Kremer T ... -  《INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE》

Targeting TGF-beta in human keratinocytes and its potential role in wound healing.

Philipp K ，Riedel F ，Sauerbier M ，Hörmann K ，Germann G ... -  《INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE》

TGF-beta antisense oligonucleotides modulate expression of matrix metalloproteinases in isolated fibroblasts from radiated skin.

Riedel K ，Kremer T ，Ryssel H ，Riedel F ，Goessler UR ，Koellensperger E ，Germann G ，Sauerbier M ... -  《IN VIVO》

TGF-beta antisense oligonucleotides reduce mRNA expression of matrix metalloproteinases in cultured wound-healing-related cells.

Philipp K ，Riedel F ，Germann G ，Hörmann K ，Sauerbier M ... -  《INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE》