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HTRA1在血管异常相关疾病中的作用及机制研究进展

Progress in the Study of the Role and Mechanism of HTRA1 in Diseases Related to Vascular Abnormalities.

作者信息

Song Shina, Li Xiaofeng, Xue Xuting, Dong Wenping, Li Changxin

机构信息

Department of Neurology, The First Hospital of Shanxi Medical University, Taiyuan, People's Republic of China.

Department of Geriatrics, General Hospital of TISCO, Taiyuan, People's Republic of China.

出版信息

Int J Gen Med. 2024 Apr 18;17:1479-1491. doi: 10.2147/IJGM.S456912. eCollection 2024.

Abstract

High temperature requirement A1 (HTRA1) is a member of the serine protease family, comprising four structural domains: IGFBP domain, Kazal domain, protease domain and PDZ domain. HTRA1 encodes a serine protease, a secreted protein that is widely expressed in the vasculature. HTRA1 regulates a wide range of physiological processes through its proteolytic activity, and is also involved in a variety of vascular abnormalities-related diseases. This article reviews the role of HTRA1 in the development of vascular abnormalities-related hereditary cerebral small vessel disease (CSVD), age-related macular degeneration (AMD), tumors and other diseases. Through relevant research advances to understand the role of HTRA1 in regulating signaling pathways or refolding, translocation, degradation of extracellular matrix (ECM) proteins, thus directly or indirectly regulating angiogenesis, vascular remodeling, and playing an important role in vascular homeostasis, further understanding the mechanism of HTRA1's role in vascular abnormality-related diseases is important for HTRA1 to be used as a therapeutic target in related diseases.

摘要

高温需求蛋白A1(HTRA1)是丝氨酸蛋白酶家族的成员,由四个结构域组成:胰岛素样生长因子结合蛋白(IGFBP)结构域、卡扎尔(Kazal)结构域、蛋白酶结构域和PDZ结构域。HTRA1编码一种丝氨酸蛋白酶,这是一种在脉管系统中广泛表达的分泌蛋白。HTRA1通过其蛋白水解活性调节多种生理过程,还参与多种与血管异常相关的疾病。本文综述了HTRA1在与血管异常相关的遗传性脑小血管病(CSVD)、年龄相关性黄斑变性(AMD)、肿瘤及其他疾病发生发展中的作用。通过相关研究进展来了解HTRA1在调节信号通路或细胞外基质(ECM)蛋白的重折叠、易位、降解中的作用,从而直接或间接调节血管生成、血管重塑,并在血管稳态中发挥重要作用,进一步了解HTRA1在与血管异常相关疾病中的作用机制对于将HTRA1用作相关疾病的治疗靶点具有重要意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0208/11034561/1085c47ac43b/IJGM-17-1479-g0001.jpg

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