综述 Review

Kallistatin的生物学作用及机制研究进展

Published at: 2015年第35卷第2期

詹丽君 1 , 卿国忠 1
1 南华大学附属第一医院急诊科,湖南 衡阳 421001
通讯作者 国忠 卿 Email: gzqing9923@163.com
DOI: 10.3978/j.issn.2095-6959.10.3978/j.issn.2095-6959.2015.02.033
基金:

摘要

人组织激肽释放酶结合蛋白(Kallistatin,KS)是一种丝氨酸蛋白酶抑制剂,最早发现具有与组织型 激肽释放酶(tissue Kallikrein,TK)特异性结合并抑制TK的功能。近年研究发现KS具有抗炎、抗 氧化应激、抗血管生成及抗肿瘤等广泛的生物学作用,作用机制与其肝素结合结构域密切相关。 KS可通过其肝素结合结构域竞争性抑制TNF-α、HMGB1与相应的内皮细胞表面受体结合,从而 抑制其介导的炎性细胞因子的表达;竞争性抑制VEGF、bEGF与其受体结合,从而抑制肿瘤血管 生成。KS通过参与调控多条细胞信号通路发挥抗氧化应激作用。KS还能够调节内皮细胞功能,诱 导肿瘤细胞凋亡。KS具有多种生物学作用,具有广阔的应用前景,尤其对于需要多靶点治疗的疾 病,如脓毒症具有潜在的治疗价值。其生物学作用机制仍需进一步研究,本文就KS的主要生物学 作用及其作用机制的最新研究进展进行阐述。


Advances in the biological effects and mechanism of Kallistatin

Abstract

Human tissue kallikrein-binding protein (Kallistatin, KS) was first found to bind to tissue kallikrein (TK) and inhibit its function as a serine protease inhibitor (SERPIN). Recent studies found that KS has extensive biological effects including anti-inflammation, oxidation resistance, anti-angiogenesis and anti-tumor activities; its mechanism is closely related to its heparin-binding domain. KS can competitively inhibit TNF-α or HMGB1 binding to its corresponding endothelial cell surface receptor via its heparin-binding domain, thereby inhibiting expression of inflammatory cytokines mediated by TNF-α or HMGB1. KS can also competitively inhibit VEGF or bEGF binding to its receptor, thereby inhibiting VEGF or bEGF mediated tumor angiogenesis. KS plays a role in oxidative stress by involving in the regulation of several cell signaling pathways. KS can also regulate endothelial cell function and induce tumor cell apoptosis. With a variety of biological activities, KS has broad application prospects. Especially for multi-target therapy of disease such as sepsis, KS has potential therapeutic value. Its biological mechanism needs further research. In this paper, the latest research progress in biological effects and mechanism of KS will be elaborated.


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引用

引用本文: 丽君 詹, 国忠 卿. Kallistatin的生物学作用及机制研究进展[J]. 临床与病理杂志, 2015, 35(2): 319-323.
Cite this article as: ZHAN Lijun, QING Guozhong . Advances in the biological effects and mechanism of Kallistatin[J]. Journal of Clinical and Pathological Research, 2015, 35(2): 319-323.