组织激肽释放酶家族在病原微生物感染中的作用

doi:10.19982/j.issn.1000-6621.20230377

摘要/Abstract

摘要：

组织激肽释放酶(tissue kallikrein-related peptidase, KLK)家族是丝氨酸蛋白酶家族中一种具有胰蛋白酶或胰凝乳蛋白酶性质的蛋白水解酶亚群,有15个家族蛋白,分别为KLK1~KLK15。近年来,越来越多的研究表明,KLK家族可通过切割病毒和细菌关键蛋白、激活多种宿主受体、调控激肽系统等方式参与机体的多种生理活动,影响着病毒、细菌和真菌中多种病原微生物感染的进程,作用机制复杂且广泛。本文通过对近年来KLK家族蛋白在微生物感染中的作用和机制进行综述,以更好地探究KLK在微生物感染中的重要作用,特别是为其在结核分枝杆菌感染中的研究提供思路,也为KLK家族蛋白作为抗结核治疗靶点提供理论基础。

关键词: 病原, 分枝杆菌,结核, 感染, 组织激肽释放酶类, 综述文献(主题)

Abstract:

Tissue kallikrein-related peptidase (KLK) is a subgroup of proteolytic enzymes with trypsin or chymotrypsin properties in the serine protease family, consisting of 15 family proteins, respectively named as KLK1 to KLK15. In recent years, more and more studies have shown that KLK can participate in various physiological activities by cutting key proteins of viruses and bacteria, activating various host receptors, regulating the kinin system, etc., affecting the course of affecting the course of various pathogenic microorganisms infection in viruses, bacteria and fungi, and the mechanism of action is complex and extensive. In this paper, the role and mechanism of KLK family proteins in microbial infection in recent years were reviewed, so as to better explore the important role of KLK in microbial infection, especially to provide ideas for their research in Mycobacterium tuberculosis infection, and to provide a theoretical basis for KLK family proteins to be used as anti-tuberculosis therapeutic targets.

Key words: Noxae, Mycobacterium tuberculosis, Infection, Tissue kallikreins, Review literature as topic

中图分类号:

尚雪恬, 潘丽萍. 组织激肽释放酶家族在病原微生物感染中的作用[J]. 中国防痨杂志, 2024, 46(2): 239-244. doi: 10.19982/j.issn.1000-6621.20230377

Shang Xuetian, Pan Liping. Role of tissue kallikrein family in pathogenesis of microorganism infection[J]. Chinese Journal of Antituberculosis, 2024, 46(2): 239-244. doi: 10.19982/j.issn.1000-6621.20230377

图/表 1

表1

参考文献 43

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病原体	KLK	疾病	作用	机制
病毒
流感病毒	KLK1、KLK5、 KLK12	流感	促进病毒感染细胞	裂解HA分子,并增强了病毒在细胞中的复制,从而增强了病毒的载量
人乳头瘤病毒	KLK8	各种疣	促进病毒感染细胞	切割HPV主要衣壳蛋白L1,引起构象变化,使小衣壳蛋白L2暴露重要表位,促进病毒脱壳进入宿主细胞
冠状病毒	KLK13	肺炎	促进病毒感染	裂解HCoV-HKU S蛋白的S1/S2区域促进病毒的感染
鼻病毒	KLK1	气道炎症	加重气道炎症	促进气道中激肽生成
细菌
结核分枝杆菌	KLK1	结核病	区分潜伏感染和活动性结核病	可能通过调节宿主KKS系统和其他分子信号通路影响疾病进程
牛分枝杆菌	KLK12	牛结核病	保护性免疫、区分潜伏感染和活动性结核病	通过mTOR/MAPK/TSC2和BAX/Bcl-2/Cytc/Caspase3通路调节自噬、凋亡和促炎症因子释放;诱导KLK12上调,与B1R/B2R相互作用,启动ERK信号通路,致MMP1和MMP9分子上调,在肉芽肿形成中起着重要作用
金黄色葡萄球菌	KLK6、KLK13、 KLK14	特应性皮炎	使皮炎加重	降解角质形成细胞的桥粒芯糖蛋白-1(desmoglein-1, DSG-1)和中间丝蛋白
牙龈卟啉单胞菌	KLK13	牙周炎	使牙周炎加重	降解KLK13抑制剂SPINK6
脑膜炎奈瑟菌	KLK1	脑膜炎	干扰细菌定植	KLK1裂解细菌表面NHBA抗原,干扰细菌定植
真菌
念珠菌	KLK1	肾损伤	保护肾脏	KLK1激活的KKS系统在念珠菌感染中发挥保护肾脏的重要作用