The effects of TGF-β type I receptor inhibitor on scar hyperplasia in vivo

碩士 === 國防醫學院 === 生物及解剖學研究所 === 105 === Skin is the largest organ of the human body, can form a protective barrier, and avoid to exogenous pathogens and injuries. When the maturation/remodeling phase of wound healing process is interfered, it may result in excessive accumulation of ECM, named scar hy...

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Main Authors: LIN, CHIEN-WEN, 林建文
Other Authors: WANG, YI-WEN
Format: Others
Language:zh-TW
Published: 2017
Online Access:http://ndltd.ncl.edu.tw/handle/25234121090298416698
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spelling ndltd-TW-105NDMC05890062017-08-26T04:27:52Z http://ndltd.ncl.edu.tw/handle/25234121090298416698 The effects of TGF-β type I receptor inhibitor on scar hyperplasia in vivo 探討乙型轉形生長因子第一型受體抑制劑對於兔耳疤痕增生之影響 LIN, CHIEN-WEN 林建文 碩士 國防醫學院 生物及解剖學研究所 105 Skin is the largest organ of the human body, can form a protective barrier, and avoid to exogenous pathogens and injuries. When the maturation/remodeling phase of wound healing process is interfered, it may result in excessive accumulation of ECM, named scar hyperplasia. That leads to skin appearance change and physiological displeasure, furthermore, the functional disorders. TGF-β is a multifunctional protein, which are involved in the functional regulation of cell: proliferation, differentiation, apoptosis, extracellular matrix production, and immune-regulation. It has been shown that excessive scarring was mainly related to over-activation of TGF-β signaling. Through the binding of TGF-β and its receptors, the downstream signaling protein Smad2/3 are phosphorylated, and then translocate into the nucleus to regulate gene transcription. TGF-β receptors inhibitor is one of the treatment strategies to inhibit the TGF-β signaling pathway. LY-364947 is known a highly specific TGF-βRI inhibitor, which inhibits phosphorylation of Smad2. Therefore, this study aimed to explore whether LY-364947 has an improved effect on the proliferation of scar. In this study, we used topical application or injection of LY-364947 on New Zealand white rabbits scar model. The wound appearance was evaluated by using the Visual analogue scale (VAS) and the Vancouver scar scale (VSS). After sacrificing animals, the scar tissues were stained with Masson's trichrome stain to observe the collagen expression. In addition, the expression levels of Smad2/3, pSmad2/3, α-SMA and CTGF were detected by Western Blot. Our results showed that the injection of LY-364947 (50 μM) and topical application of LY-364947 (250 μM) were improved the appearance of the scar in the early stage. In the Masson’s trichrome stain, the expression of collagen fibers in the dermis layer was decreased in the early stage of LY-364947 treatment group. In addition, the expression of pSmad2/3 was lower in the LY-364947 treatment group, while α-SMA and CTGF was lightly increased. Base on these results, we suggest that LY-364947 might have the function of inhibition in scar hyperplasia, however the treatment dosage and period need to be optimized. WANG, YI-WEN MA, KUO-HSING 王怡文 馬國興 2017 學位論文 ; thesis 58 zh-TW
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description 碩士 === 國防醫學院 === 生物及解剖學研究所 === 105 === Skin is the largest organ of the human body, can form a protective barrier, and avoid to exogenous pathogens and injuries. When the maturation/remodeling phase of wound healing process is interfered, it may result in excessive accumulation of ECM, named scar hyperplasia. That leads to skin appearance change and physiological displeasure, furthermore, the functional disorders. TGF-β is a multifunctional protein, which are involved in the functional regulation of cell: proliferation, differentiation, apoptosis, extracellular matrix production, and immune-regulation. It has been shown that excessive scarring was mainly related to over-activation of TGF-β signaling. Through the binding of TGF-β and its receptors, the downstream signaling protein Smad2/3 are phosphorylated, and then translocate into the nucleus to regulate gene transcription. TGF-β receptors inhibitor is one of the treatment strategies to inhibit the TGF-β signaling pathway. LY-364947 is known a highly specific TGF-βRI inhibitor, which inhibits phosphorylation of Smad2. Therefore, this study aimed to explore whether LY-364947 has an improved effect on the proliferation of scar. In this study, we used topical application or injection of LY-364947 on New Zealand white rabbits scar model. The wound appearance was evaluated by using the Visual analogue scale (VAS) and the Vancouver scar scale (VSS). After sacrificing animals, the scar tissues were stained with Masson's trichrome stain to observe the collagen expression. In addition, the expression levels of Smad2/3, pSmad2/3, α-SMA and CTGF were detected by Western Blot. Our results showed that the injection of LY-364947 (50 μM) and topical application of LY-364947 (250 μM) were improved the appearance of the scar in the early stage. In the Masson’s trichrome stain, the expression of collagen fibers in the dermis layer was decreased in the early stage of LY-364947 treatment group. In addition, the expression of pSmad2/3 was lower in the LY-364947 treatment group, while α-SMA and CTGF was lightly increased. Base on these results, we suggest that LY-364947 might have the function of inhibition in scar hyperplasia, however the treatment dosage and period need to be optimized.
author2 WANG, YI-WEN
author_facet WANG, YI-WEN
LIN, CHIEN-WEN
林建文
author LIN, CHIEN-WEN
林建文
spellingShingle LIN, CHIEN-WEN
林建文
The effects of TGF-β type I receptor inhibitor on scar hyperplasia in vivo
author_sort LIN, CHIEN-WEN
title The effects of TGF-β type I receptor inhibitor on scar hyperplasia in vivo
title_short The effects of TGF-β type I receptor inhibitor on scar hyperplasia in vivo
title_full The effects of TGF-β type I receptor inhibitor on scar hyperplasia in vivo
title_fullStr The effects of TGF-β type I receptor inhibitor on scar hyperplasia in vivo
title_full_unstemmed The effects of TGF-β type I receptor inhibitor on scar hyperplasia in vivo
title_sort effects of tgf-β type i receptor inhibitor on scar hyperplasia in vivo
publishDate 2017
url http://ndltd.ncl.edu.tw/handle/25234121090298416698
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