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基底膜衍生的基质隐窝蛋白在心脏中作用的新见解

New Insights into the Role of Basement Membrane-Derived Matricryptins in the Heart.

作者信息

Okada Muneyoshi, Imoto Keisuke, Sugiyama Akira, Yasuda Jumpei, Yamawaki Hideyuki

机构信息

Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University.

出版信息

Biol Pharm Bull. 2017;40(12):2050-2060. doi: 10.1248/bpb.b17-00308.

Abstract

The extracellular matrix (ECM), which contributes to structural homeostasis as well as to the regulation of cellular function, is enzymatically cleaved by proteases, such as matrix metalloproteinases and cathepsins, in the normal and diseased heart. During the past two decades, matricryptins have been defined as fragments of ECM with a biologically active cryptic site, namely the 'matricryptic site,' and their biological activities have been initially identified and clarified, including anti-angiogenic and anti-tumor effects. Thus, matricryptins are expected to be novel anti-tumor drugs, and thus widely investigated. Although there are a smaller number of studies on the expression and function of matricryptins in fields other than cancer research, some matricryptins have been recently clarified to have biological functions beyond an anti-angiogenic effect in heart. This review particularly focuses on the expression and function of basement membrane-derived matricryptins, including arresten, canstatin, tumstatin, endostatin and endorepellin, during cardiac diseases leading to heart failure such as cardiac hypertrophy and myocardial infarction.

摘要

细胞外基质(ECM)对结构稳态以及细胞功能的调节均有作用,在正常和患病心脏中,它会被蛋白酶(如基质金属蛋白酶和组织蛋白酶)酶解。在过去二十年中,基质隐窝蛋白被定义为具有生物活性隐蔽位点(即“基质隐窝位点”)的ECM片段,其生物活性最初已被鉴定和阐明,包括抗血管生成和抗肿瘤作用。因此,基质隐窝蛋白有望成为新型抗肿瘤药物,并因此受到广泛研究。尽管在癌症研究以外的领域,关于基质隐窝蛋白表达和功能的研究较少,但最近已明确一些基质隐窝蛋白在心脏中具有超出抗血管生成作用的生物学功能。本综述特别关注在导致心力衰竭的心脏疾病(如心脏肥大和心肌梗死)过程中,源自基底膜的基质隐窝蛋白(包括抑制素、制瘤素、tumstatin、内皮抑素和内源性趋化素)的表达和功能。

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