Kikuchi Alexander, Monga Satdarshan Pal
Department of Pathology and Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Gene Expr. 2015;16(3):109-27. doi: 10.3727/105221615X14181438356210.
Platelet-derived growth factor receptor α (PDGFRα) is an isoform of the PDGFR family of tyrosine kinase receptors involved in cell proliferation, survival, differentiation, and growth. In this review, we highlight the role of PDGFRα and the current evidence of its expression and activities in liver development, regeneration, and pathology-including fibrosis, cirrhosis, and liver cancer. Studies elucidating PDGFRα signaling in processes ranging from profibrotic signaling, angiogenesis, and oxidative stress to epithelial-to-mesenchymal transition point toward PDGFRα as a potential therapeutic target in various hepatic pathologies, including hepatic fibrosis and liver cancer. Furthermore, PDGFRα localization and modulation during liver development and regeneration may lend insight into its potential roles in various pathologic states. We will also briefly discuss some of the current targeted treatments for PDGFRα, including multi receptor tyrosine kinase inhibitors and PDGFRα-specific inhibitors.
血小板衍生生长因子受体α(PDGFRα)是酪氨酸激酶受体PDGFR家族的一种亚型,参与细胞增殖、存活、分化和生长。在本综述中,我们重点介绍了PDGFRα的作用以及其在肝脏发育、再生和病理学(包括纤维化、肝硬化和肝癌)中表达及活性的现有证据。阐明PDGFRα信号传导在从促纤维化信号传导、血管生成、氧化应激到上皮-间质转化等过程中的研究表明,PDGFRα是包括肝纤维化和肝癌在内的各种肝脏疾病的潜在治疗靶点。此外,PDGFRα在肝脏发育和再生过程中的定位和调节可能有助于深入了解其在各种病理状态下的潜在作用。我们还将简要讨论目前针对PDGFRα的一些靶向治疗方法,包括多受体酪氨酸激酶抑制剂和PDGFRα特异性抑制剂。