Furuichi H, Yamashita K, Okada M, Toyoshima T, Hata Y, Suzuki S, Itano T, Shishibori T, Tokumitsu H, Kobayashi R
Department of Chemistry, Kagawa Medical University, Kagawa, 761-0793, Japan.
Biochem Biophys Res Commun. 2000 Apr 21;270(3):1002-8. doi: 10.1006/bbrc.2000.2480.
To elucidate the molecular mechanism involved in the suppression of keloids and hypertrophic scars by tranilast, we investigated the target protein of tranilast in bovine skin and aorta. A specific tranilast-binding protein was isolated from both tissues by drug affinity chromatography and was identified as 36-kDa microfibril-associated glycoprotein (36-kDa MAGP). Binding of 36-kDa MAGP to tranilast seemed to be specific since 36-kDa MAGP could be eluted from the drug affinity column by tranilast itself and also binding of 36-kDa MAGP to other anti-allergy drugs (amlexanox and cromolyn) is significantly weaker than that to tranilast. Light and electron microscopic immunohistochemistry detected the protein at the periphery of elastic fibers in normal human skin. In hypertrophic scar tissue, however, 36-kDa MAGP was located on small bundles of microfibrils. These findings provide support for the concept that elastogenesis occurs in scar tissue and 36-kDa MAGP might be one of the targets for tranilast.
为阐明曲尼司特抑制瘢痕疙瘩和增生性瘢痕的分子机制，我们研究了曲尼司特在牛皮肤和主动脉中的靶蛋白。通过药物亲和色谱法从这两种组织中分离出一种特异性的曲尼司特结合蛋白，鉴定为36 kDa微原纤维相关糖蛋白（36 kDa MAGP）。36 kDa MAGP与曲尼司特的结合似乎具有特异性，因为36 kDa MAGP可被曲尼司特自身从药物亲和柱上洗脱下来，而且36 kDa MAGP与其他抗过敏药物（氨来呫诺和色甘酸）的结合明显弱于与曲尼司特的结合。光镜和电镜免疫组织化学检测发现该蛋白位于正常人皮肤弹性纤维的周边。然而，在增生性瘢痕组织中，36 kDa MAGP位于微原纤维小束上。这些发现支持了瘢痕组织中发生弹性纤维生成的概念，并且36 kDa MAGP可能是曲尼司特的靶标之一。
