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特发性肺纤维化(IPF)治疗中 LPA-LPAR1 和 VEGF-VEGFR2 信号通路的抑制作用。

Inhibition of LPA-LPAR1 and VEGF-VEGFR2 Signaling in IPF Treatment.

机构信息

Gansu University Key Laboratory for Molecular Medicine and Chinese Medicine Prevention and Treatment of Major Diseases, Gansu University of Chinese Medicine, Lanzhou, 730000, People's Republic of China.

出版信息

Drug Des Devel Ther. 2023 Sep 2;17:2679-2690. doi: 10.2147/DDDT.S415453. eCollection 2023.

Abstract

Due to the complex mechanism and limited treatments available for pulmonary fibrosis, the development of targeted drugs or inhibitors based on their molecular mechanisms remains an important strategy for prevention and treatment. In this paper, the downstream signaling pathways mediated by VEGFR and LPAR1 in pulmonary cells and the role of these pathways in pulmonary fibrosis, as well as the current status of drug research on the targets of LPAR1 and VEGFR2, are described. The mechanism by which these two pathways regulate vascular leakage and collagen deposition leading to the development of pulmonary fibrosis are analyzed, and the mutual promotion of the two pathways is discussed. Here we propose the development of drugs that simultaneously target LPAR1 and VEGFR2, and discuss the important considerations in targeting and safety.

摘要

由于肺纤维化的发病机制复杂,治疗方法有限,因此基于其分子机制开发靶向药物或抑制剂仍然是预防和治疗的重要策略。本文描述了 VEGFR 和 LPAR1 在肺细胞中介导的下游信号通路及其在肺纤维化中的作用,以及 LPAR1 和 VEGFR2 靶点的药物研究现状。分析了这两条通路调节血管渗漏和胶原沉积导致肺纤维化发展的机制,并讨论了两条通路的相互促进作用。在此,我们提出了同时针对 LPAR1 和 VEGFR2 的药物开发,并讨论了靶向治疗和安全性的重要考虑因素。

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