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用于治疗肝脏疾病的潜在疗法的 Ephrin-Eph 受体酪氨酸激酶

Ephrin-Eph receptor tyrosine kinases for potential therapeutics against hepatic pathologies.

作者信息

Mekala Sowmya, Dugam Prachi, Das Amitava

机构信息

Department of Applied Biology, Council of Scientific and Industrial Research-Indian Institute of Chemical Technology (CSIR-IICT), Uppal Road, Tarnaka, Hyderabad, TS, 500 007, India.

Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, UP, 201 002, India.

出版信息

J Cell Commun Signal. 2023 Sep;17(3):549-561. doi: 10.1007/s12079-023-00750-1. Epub 2023 Apr 27.

Abstract

Hepatic fibrosis is the common pathological change that occurs due to increased synthesis and accumulation of extracellular matrix components. Chronic insult from hepatotoxicants leads to liver cirrhosis, which if not reversed timely using appropriate therapeutics, liver transplantation remains the only effective therapy. Often the disease further progresses into hepatic carcinoma. Although there is an increased advancement in understanding the pathological phenotypes of the disease, additional knowledge of the novel molecular signaling mechanisms involved in the disease progression would enable the development of efficacious therapeutics. Ephrin-Eph molecules belong to the largest family of receptor tyrosine kinases (RTKs) which are identified to play a crucial role in cellular migratory functions, during morphological and developmental stages. Additionally, they contribute to the growth of a multicellular organism as well as in pathological conditions like cancer, and diabetes. A wide spectrum of mechanistic studies has been performed on ephrin-Eph RTKs in various hepatic tissues under both normal and diseased conditions revealing their diverse roles in hepatic pathology. This systematic review summarizes the liver-specific ephrin-Eph RTK signaling mechanisms and recognizes them as druggable targets for mitigating hepatic pathology.

摘要

肝纤维化是由于细胞外基质成分合成增加和积累而发生的常见病理变化。肝毒性物质的慢性损伤会导致肝硬化,如果不及时使用适当的治疗方法逆转,肝移植仍然是唯一有效的治疗方法。这种疾病常常会进一步发展为肝癌。尽管在理解该疾病的病理表型方面有了更多进展,但对疾病进展中涉及的新型分子信号机制的更多了解将有助于开发有效的治疗方法。Ephrin-Eph分子属于最大的受体酪氨酸激酶(RTK)家族,已确定它们在形态和发育阶段的细胞迁移功能中起关键作用。此外,它们有助于多细胞生物体的生长以及在癌症和糖尿病等病理状况中发挥作用。在正常和患病条件下,已经对各种肝组织中的ephrin-Eph RTK进行了广泛的机制研究,揭示了它们在肝脏病理学中的多种作用。本系统综述总结了肝脏特异性ephrin-Eph RTK信号传导机制,并将它们识别为减轻肝脏病理学的可药物作用靶点。

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本文引用的文献

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