Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Higashi 23 Bancho 35-1, Towada City, Aomori 034-8628, Japan.
Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Higashi 23 Bancho 35-1, Towada City, Aomori 034-8628, Japan.
J Pharmacol Sci. 2019 Feb;139(2):59-64. doi: 10.1016/j.jphs.2018.12.001. Epub 2018 Dec 10.
Type IV collagen is a main component of basement membrane extracellular matrix. Canstatin, a non-collagenous C-terminal fragment of type IV collagen α2 chain, was firstly identified as an endogenous anti-angiogenic and anti-tumor factor, which also has an anti-lymphangiogenic effect. Then, canstatin has been widely investigated as a novel target molecule for cancer therapy. The anti-angiogenic effect of canstatin may be also useful for the treatment of ocular neovascularization. Recently, we have demonstrated that canstatin, which is abundantly expressed in the heart tissue, exerts various biological activities in cardiac cells. In rat H9c2 cardiomyoblasts, canstatin inhibits isoproterenol- or hypoxia-induced apoptosis. Canstatin plays an important role in modulating voltage-dependent calcium channel activity in rat cardiomyocytes. Canstatin also regulates various biological functions in rat cardiac fibroblasts and myofibroblasts. The expression of canstatin decreases in the infarcted area after myocardial infarction. This review focuses on a current perspective for the roles of canstatin in tumorigenesis, ocular neovascularization and cardiac pathology.
IV 型胶原是基底膜细胞外基质的主要成分。Canstatin 是 IV 型胶原 α2 链的非胶原 C 端片段，最初被鉴定为一种内源性抗血管生成和抗肿瘤因子，也具有抗淋巴管生成作用。随后，Canstatin 被广泛研究作为癌症治疗的新型靶标分子。Canstatin 的抗血管生成作用对于治疗眼部新生血管化也可能有用。最近，我们已经证明，在心脏组织中大量表达的 Canstatin 在心肌细胞中发挥多种生物学活性。在大鼠 H9c2 心肌细胞中，Canstatin 抑制异丙肾上腺素或缺氧诱导的细胞凋亡。Canstatin 在调节大鼠心肌细胞电压依赖性钙通道活性方面发挥重要作用。Canstatin 还调节大鼠心脏成纤维细胞和肌成纤维细胞的各种生物学功能。心肌梗死后，Canstatin 在梗死区的表达减少。这篇综述重点介绍了 Canstatin 在肿瘤发生、眼部新生血管化和心脏病理学中的作用的最新观点。
