Yamada H, Tajima S, Nishikawa T, Murad S, Pinnell S R
Department of Dermatology, Keio University School of Medicine, Tokyo.
J Biochem. 1994 Oct;116(4):892-7. doi: 10.1093/oxfordjournals.jbchem.a124612.
Effects of tranilast, N-(3,4-dimethoxycinnamoyl)anthranilic acid, on collagen synthesis in cultured human skin fibroblasts were studied. Tranilast was found to inhibit collagen synthesis in a dose-dependent manner to a maximum of 55% at 300 microM during 48 h of treatment; the synthesis of type I and type III collagens was equally affected. Administered simultaneously or subsequently, tranilast reduced the stimulatory effect of transforming growth factor beta 1 (2.5 ng/ml) on collagen synthesis without affecting the accompanying stimulation of noncollagen protein synthesis. It did not affect prolyl or lysyl hydroxylase activity in vitro and in cells. The content of pro alpha 1(I) collagen mRNA was decreased 60% by tranilast. Tranilast prevented the TGF beta 1-mediated increase in pro alpha 1(I) collagen mRNA. These results indicate that tranilast specifically inhibits collagen production at a pretranslational level by interfering with TGF beta 1 effects. Tranilast also inhibited collagen synthesis in scleroderma fibroblasts to the same extent and in keloid fibroblasts to a greater extent than in normal fibroblasts, attesting to its therapeutic potential as an antifibrotic drug.
研究了曲尼司特（N-(3,4-二甲氧基肉桂酰)邻氨基苯甲酸）对培养的人皮肤成纤维细胞中胶原蛋白合成的影响。发现曲尼司特在处理48小时期间以剂量依赖性方式抑制胶原蛋白合成，在300 microM时最大抑制率为55%；I型和III型胶原蛋白的合成受到同等影响。同时或随后给予曲尼司特，可降低转化生长因子β1（2.5 ng/ml）对胶原蛋白合成的刺激作用，而不影响伴随的非胶原蛋白合成刺激。它在体外和细胞中均不影响脯氨酰或赖氨酰羟化酶活性。曲尼司特使原α1(I)胶原蛋白mRNA含量降低60%。曲尼司特可防止TGFβ1介导的原α1(I)胶原蛋白mRNA增加。这些结果表明，曲尼司特通过干扰TGFβ1的作用，在翻译前水平特异性抑制胶原蛋白产生。曲尼司特对硬皮病成纤维细胞中胶原蛋白合成的抑制程度与正常成纤维细胞相同，对瘢痕疙瘩成纤维细胞的抑制程度更大，证明其作为抗纤维化药物的治疗潜力。
