Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.
Division of Regenerative Biology, School of Biomedical Sciences, University of Western Australia, Perth, WA, Australia.
Cell Prolif. 2020 Feb;53(2):e12746. doi: 10.1111/cpr.12746. Epub 2019 Dec 22.
Human high-temperature requirement protein 1 (HTRA1) is a member of serine proteases and consists of four well-defined domains-an IGFBP domain, a Kazal domain, a protease domain and a PDZ domain. HTRA1 is a secretory protein and also present intracellularly and associated with microtubules. HTRA1 regulates a broad range of physiological processes via its proteolytic activity. This review examines the role of HTRA1 in bone biology, osteoarthritis, intervertebral disc (IVD) degeneration and tumorigenesis. HTRA1 mediates diverse pathological processes via a variety of signalling pathways, such as TGF-β and NF-κB. The expression of HTRA1 is increased in arthritis and IVD degeneration, suggesting that HTRA1 protein is attributed to cartilage degeneration and disease progression. Emerging evidence also suggests that HTRA1 has a role in tumorigenesis. Further understanding the mechanisms by which HTRA1 displays as an extrinsic and intrinsic regulator in a cell type-specific manner will be important for the development of HTRA1 as a therapeutic target.
人高热需求蛋白 1（HTRA1）是丝氨酸蛋白酶家族的一员，由四个明确的结构域组成-IGFBP 结构域、Kazal 结构域、蛋白酶结构域和 PDZ 结构域。HTRA1 是一种分泌蛋白，也存在于细胞内，并与微管相关。HTRA1 通过其蛋白水解活性调节广泛的生理过程。本综述探讨了 HTRA1 在骨生物学、骨关节炎、椎间盘（IVD）退变和肿瘤发生中的作用。HTRA1 通过多种信号通路（如 TGF-β 和 NF-κB）介导多种病理过程。HTRA1 在关节炎和 IVD 退变中的表达增加，表明 HTRA1 蛋白与软骨退变和疾病进展有关。新出现的证据还表明，HTRA1 在肿瘤发生中起作用。进一步了解 HTRA1 作为细胞类型特异性的外在和内在调节剂的作用机制，对于将 HTRA1 作为治疗靶点的开发将是重要的。
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