乙酰肝素酶与相关疾病的研究进展

Research Progress of Heparanase and Related Diseases

乙酰肝素酶(HPA)是人体内唯一能降解硫酸肝素蛋白多糖(HSPG)的一种β-D-葡萄糖醛酸内切酶。HSPG是细胞外基质(ECM)的重要组成部分,广泛分布于细胞表面,在正常组织的发育与病理学改变的发展中具有重要作用。HPA能识别HSPG的硫酸肝素链(HS)并将其降解,进而影响ECM与上皮细胞及内皮细胞基底膜结构,释放与HSPG结合的各种细胞因子。除通过降解HS产生间接生理作用外,HPA还以聚集、脱落、分裂素绑定的方式影响多配体聚糖的生物效应。另外,HPA可以增强信号级联效应,促进蛋白激酶的磷酸化和基因转录。因此,HPA的激活会引起一些病理生理学改变,包括炎性反应、血管形成、肿瘤转移、胚胎植入等。笔者拟就HPA与相关疾病的研究进展,进行综述如下。

The heparanase （HPA）,aβ-D-glucuronidase enzyme,is an unique enzyme of the human body to degrade heparan sulfate proteoglycan （HSPG）.HSPG,an important part of extracellular matrix （ECM）and widely distributed on the cell surface,plays an important role in the process of growth and development of normal and pathological tissues.HPA can identify heparan sulfate （HS）chains of HSPG and degrade them,thereby affects the ECM and basement membrane of epithelial cells and endothelial cells. So various cytokines binded with HSPG are released.In addition to the indirect physiological effects through degrading HS,HPA also can affect the biological effects of syndecan by aggregating,shedding,binding mitogens ligands.Furthermore,HPA can enhance the signal-cascading effect,promote the phosphorylation of the protein kinase and gene transcription.Therefore,the activation of HPA will cause some of the pathophysiological changes,including inflammation,angiogenesis,tumor metastasis,embryo implantation. This article reviews the progress of HPA and related diseases.