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血小板衍生生长因子的致病机制及作为治疗靶点的可能性

Pathogenetic significance and possibility as a therapeutic target of platelet derived growth factor.

作者信息

Ishii Yoko, Hamashima Takeru, Yamamoto Seiji, Sasahara Masakiyo

机构信息

Department of Pathology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan.

出版信息

Pathol Int. 2017 May;67(5):235-246. doi: 10.1111/pin.12530. Epub 2017 Apr 10.

Abstract

Platelet-derived growth factor (PDGF) is one of the major mitogens and chemoattractants for mesenchymal and glial cells. Nowadays, the expression of PDGFs are recognized widely in our body, and emerging data indicate the relevance of PDGFs in the homeostatic control of systemic connective tissue as well as parenchymal cells such as neurons. Aberrant PDGF signal is primarily tumorigenic, and also regulates tumor microenvironments. The roles of the PDGF signal in tumorigenesis are diverse depending on the type of cancer, and anti-PDGF therapy needs to be carefully designed based on the information of each tumor cell type and the surrounding microenvironment. PDGFs and receptors (PDGFRs) are abundant in neurons and glial cells, and are neuroprotective through the regulation of neurovascular unit. PDGF signal is functionally correlated with neurotransmission, and can be pathogenetically correlated with psychosomatic neurological diseases. Growing genetic information has been unraveling novel connective tissue diseases and vascular abnormalities in which aberrant PDGF signaling is etiologically correlated. Novel therapeutic approaches targeting PDGF signal are beginning to emerge in various diseases.

摘要

血小板衍生生长因子(PDGF)是间充质细胞和神经胶质细胞的主要促分裂原和趋化因子之一。如今,PDGFs在我们体内的表达已得到广泛认可,并且新出现的数据表明PDGFs在全身结缔组织以及神经元等实质细胞的稳态控制中具有相关性。异常的PDGF信号主要具有致瘤性,并且还调节肿瘤微环境。PDGF信号在肿瘤发生中的作用因癌症类型而异,基于每种肿瘤细胞类型和周围微环境的信息,需要精心设计抗PDGF治疗。PDGFs及其受体(PDGFRs)在神经元和神经胶质细胞中大量存在,并通过调节神经血管单元发挥神经保护作用。PDGF信号在功能上与神经传递相关,并且在发病机制上可能与身心神经疾病相关。越来越多的基因信息揭示了新的结缔组织疾病和血管异常,其中异常的PDGF信号在病因上与之相关。针对PDGF信号的新型治疗方法开始在各种疾病中出现。

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