The effects of DMARDs on the expression and function of P-gp, MRPs, BCRP in the treatment of autoimmune diseases
The effects of DMARDs on the expression and function of P-gp, MRPs, BCRP in the treatment of autoimmune diseases
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DMARDs在自身免疫性疾病治疗中对P-gp、MRPs、BCRP表达及功能的影响
DOI：
10.1016/j.biopha.2018.06.015
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发表时间：
2018-09-01
影响因子：
7.5
通讯作者：
Wei, Wei
中科院分区：
文献类型：
--
作者：
Wu, Yi-jin;Wang, Chun;Wei, Wei
ATP结合盒（ABC）转运蛋白家族是一大类ATP能量依赖性跨膜蛋白，其主要功能是利用ATP水解产生的能量来转运与质膜结合的底物。该家族还与多种疾病的多药耐药性（MDR）密切相关。 ABC转运蛋白中，P-糖蛋白（P-gp）、多药耐药相关蛋白（MRP）和乳腺癌耐药蛋白（BCRP）是与MDR相关的主要成员。目前，这些转运蛋白在治疗失败中的作用已在癌症中得到了广泛的研究和回顾。然而，它们在自身免疫性疾病（AID）中却很少被描述。 AID是一组病因不明的慢性炎症性疾病。 AID的基本特征是产生大量自身抗体，导致多个系统、多个器官的广泛损害。疾病缓解抗风湿药物（DMARD）常用于治疗 AID，但随着时间的推移，相当多的患者对这些药物没有反应或产生耐药性。这种现象可能与ABC转运蛋白的异常表达有关，导致进入产生MDR的细胞的药物量减少。本文综述DMARDs治疗AID时对P-gp、MRPs、BCRP表达和功能的影响及其相关分子机制。
The ATP-binding cassette (ABC) transporter family is a large class of ATP energy-dependent transmembrane proteins, and its primary function is to use the energy produced by ATP hydrolysis to transfer the substrate bound to the plasma membrane. This family is also closely related to multidrug resistance (MDR) in various diseases. Among the ABC transporter proteins, P-glycoprotein (P-gp), multidrug resistance-associated protein (MRP) and breast cancer resistance protein (BCRP) are the main members associated with MDR. At present, the roles of these transporters in therapeutic failures have been extensively studied and reviewed in cancer; however, they have rarely been described in autoimmune diseases (AIDs). AID is a group of chronic inflammatory diseases of unknown aetiology. AID's basic feature is the production of a large number of autoantibodies, which leads to extensive damage to multiple systems and multiple organs. Disease-modifying anti-rheumatic drugs (DMARDs) are commonly used in the treatment of AID, but a considerable number of patients have no response or develop resistance to these drugs over time. This phenomenon may be related to the abnormal expression of the ABC transporter, which leads to a decrease in the amount of drug entering cells that produce MDR. This article reviews the effects of DMARDs on the expression and function of P-gp, MRPs, and BCRP and the related molecular mechanism in the treatment of AID.