- The Effect of Antibody and Gene Therapy for Transforming Growth Factor- 1 on Scar Formation.
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Jun Hyung Kim, Ki Hwan Han, Jong Duck Ahn, In Kyu Lee, Eun Joo Kim, Mee Yul Hwang, Kwan Kyu Park
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Korean J Pathol. 2001;35(5):424-432.
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 Abstract
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- BACKGROUND
Transforming growth factor (TGF)- has a large variety of biological functions, including the modulation of inflammation and the immune system, and is presumed to play important roles in repairing wounds and reducing scarring.
The objective of this study is to examine the effects of TGF-1 on healing wounds and reducing scarring. We have also analysed the ability of the hemagglutinating virus of Japan (HVJ) liposome mediated antisense oligodeoxynucleotides (ODNs) to specifically inhibit wound-induced expressions of TGF-1 proteins and mRNA in the rat skin.
METHODS
Skin wounds were created on the backs of 80 anesthetized rats. The first group of wounds, as the controls, was unmanipulated. The second group of wounds, as positive controls or an excessive scarring model, was injected with TGF-1 subcutaneously. The third group of wounds was injected with anti-TGF-1 antibody subcutaneously.
The fourth group of wounds was injected with HVJ liposome mediated antisense ODNs for TGF-1 subcutaneously. The wounds of all groups were bisected and analysed histologically 5, 10, 15, 30, and 50 days after the wounds were made.
RESULTS
All control wounds (TGF-1 or no injection) healed with scarring, whereas the wounds treated with the antibody or antisense ODNs healed with less scar formation compared to the control group. The wounds treated with the antibody or antisense ODNs had fewer macrophages, less collagen and fibronectin contents than the other wounds. Northern blotting and in situ hybridization analysis showed that wound sites treated with HVJ liposome mediated antisense ODNs for TGF-1 exhibited decreased levels of TGF-1 mRNA after injury.
CONCLUSIONS
These findings suggest an important new approach to controlling scarring in normal wound healing, complementing the practice of adding exogenous growth factors to chronic wounds in the attempt to inhibit collagen deposition.
- Expression of Transforming Growth Factor-beta1 in Cyclosporine-Induced Nephropathy in Rats.
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Yu Na Kang, Kwan Kyu Park, Mee Yul Hwang, Kun Young Kwon, Sang Sook Lee, Eun Sook Chang, Hyun Chul Kim
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Korean J Pathol. 2000;34(9):642-651.
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Abstract
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- Cyclosporine nephropathy was induced by intraperitoneal injection of cyclosporine 25 mg/kg in Sprague-Dawley rats daily for 1, 4, 8, and 12 weeks to clarify the relationship between cyclosporine nephropathy and the expression of TGF-beta1 with extracellular matrix deposition. On light microscopic examination, the kidneys in the 12 week cyclosporine-treated rats showed focal or striped fibrosis, vacuolization of tubular cells, and injury of endothelial cells.
Immunohistochemically, TGF-beta1 protein was strongly expressed in the cyclosporine-treated rat kidneys, especially in the glomerular endothelial cells, interstitial endothelial cells, tubular epithelial cells, and parietal cells in the Bowman's capsule of the glomerulus as well as the periglomerular arterioles. The amount of TGF-beta1 expression was correlated with the morphological change in the cyclosporine-treated rats. Extracellular matrix, such as fibronectin and collagen IV, was also expressed in the endothelial cells of the glomerulus and the interstitium. It can be concluded, therefore that TGF-beta1 protein is probably involved in the early stage of fibrogenesis in cyclosporine nephropathy. It can be postulated that cyclosporine nephropathy results from the accumulation of extracellular matrix associated with the increase of TGF-beta1 transcription. Therefore, these results could be used in reducing fibrosis in cyclosporine nephropathy.
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