Development of the novel therapeutic modality for hyperplastic scar and keloid using short chain fatty acids and polyunsaturated fatty acids

使用短链脂肪酸和多不饱和脂肪酸开发治疗增生性疤痕和疤痕疙瘩的新方法

• 批准号: 23592648
• 负责人: USAMI Makoto
• 金额: $ 3.33万
• 依托单位: Kobe University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23592648/
• 关键词: 創傷治癒学; 短鎖脂肪酸; ω-3系多価不飽和脂肪酸; ケロイド; 線維芽細胞; 細胞・組織; 脂質; 線維化

We revealed the antifibrogenic effects of short chain fatty acids and polyunsaturated fatty acids, and the best combination is butyrate and docosahexaenoic acid among those fatty acids. As the mechanisms, we found the inhibitory effects on the expressions of profibrotic factors including alpha-SMA, TGF-beta1, type I collagen and type III collagen, and the inhibition of cell proliferation, and promotion of apoptosis in normal human dermal and keloid fibroblasts. These antifibrogenic effects were also found in the pathological models with addition of proinflammatory cytokines or pseudomonas aeruginosa derived LPS or TGF-beta1 stimulation. As the key mechanisms of these effects, the production of PGE2, as an antifibrogenic lipid mediator, and the histone acetylation by butyrate were revealed.

我们发现短链脂肪酸和多不饱和脂肪酸的抗纤维化作用，其中丁酸和二十二碳六烯酸的组合效果最好。机制方面，我们发现其对正常人真皮和瘢痕疙瘩成纤维细胞中α - sma、tgf - β 1、I型胶原和III型胶原等促纤维化因子的表达有抑制作用，抑制细胞增殖，促进细胞凋亡。在添加促炎细胞因子或铜绿假单胞菌衍生的LPS或tgf - β 1刺激的病理模型中也发现了这些抗纤维化作用。作为这些作用的关键机制，PGE2的产生，作为抗纤维化的脂质介质和组蛋白乙酰化的丁酸盐被揭示。

项目成果

TGF-β1/IL-1β刺激下ケロイド線維芽細胞のapoptosis耐性および線維形成亢進に対する酪酸・DHAの制御作用

丁酸盐和DHA对TGF-β1/IL-1β刺激的瘢痕疙瘩成纤维细胞凋亡抵抗和过度纤维化的调节作用

• 发表时间: 2013
• 作者: 前重伯壮;荒木杏子;坂安優未;鳥井一宏;田淵寛人;青山倫子;三好真琴;植村弥希子;今井緑;濱田康弘;寺師浩人;宇佐美眞
• 通讯作者: 宇佐美眞

短鎖脂肪酸・多価不飽和脂肪酸がケロイド由来線維芽細胞に与える抗線維化作用

短链脂肪酸和多不饱和脂肪酸对瘢痕疙瘩来源的成纤维细胞的抗纤维化作用

• 发表时间: 2012
• 作者: 鳥井一宏;前重伯壮;青山倫子;今井緑;田淵寛人;三好真琴;濱田康弘;寺師浩人;宇佐美眞
• 通讯作者: 宇佐美眞

Antifibrogenic effects of short chain fatty acids and omega-3 polyunsaturated fatty acids on human dermal fibroblasts

短链脂肪酸和omega-3多不饱和脂肪酸对人真皮成纤维细胞的抗纤维化作用

• 发表时间: 2012
• 作者: Kazuhiro Torii;Noriaki Maeshige;Michiko Aoyama;Midori Imai;Hiroto Tabuchi;Makoto Miyoshi;Yasuhiro Hamada;Hiroto Terashi;Makoto Usami
• 通讯作者: Makoto Usami

Novel antifibrogenic therapy for keloid formation by butyrate and DHA combination; in vitro study

丁酸盐和 DHA 组合用于治疗瘢痕疙瘩形成的新型抗纤维形成疗法；

• 发表时间: 2012
• 作者: Kazuhiro Torii;Noriaki Maeshige;Michiko Aoyama;Midori Imai;Hiroto Tabuchi;Makoto Miyoshi;Yasuhiro Hamada;Hiroto Terashi;Makoto Usami
• 通讯作者: Makoto Usami

短鎖脂肪酸・多価不飽和脂肪酸がヒト皮膚由来線維芽細胞に与える抗線維化作用

短链脂肪酸和多不饱和脂肪酸对人皮肤成纤维细胞的抗纤维化作用

• 发表时间: 2012
• 作者: 鳥井一宏;前重伯壮;青山倫子;今井緑;田淵寛人;三好真琴;濱田康弘;寺師浩人;宇佐美眞
• 通讯作者: 宇佐美眞