摘要
多囊肝病(PLD)是由几个PLD相关基因突变引发的遗传疾病的一组,其特征在于存在逐渐取代肝组织的多个胆管细胞来源的肝囊肿。 PLD与常染色体显性多囊肾病(ADPKD)和常染色体隐性遗传性PKD共存,并且单独发生(即常染色体显性多囊肝病[ADPLD])。与ADPKD和ARPKD相关的PLD属于一组被称为胆管瘤病的疾病,因为许多致病和疾病相关的蛋白质在胆管细胞的原发纤毛中表达。这些蛋白质在原发性纤毛中的异常表达影响其促进膀胱发生的结构和功能。目前PLD的药物疗法包括对症治疗和外科手术。迄今为止,唯一可用于停止疾病进展和改善生活质量的PLD患者的药物治疗是生长抑素类似物。然而,适度的临床益处,长期维持治疗的需要和高昂的治疗成本证明了更有效的治疗方案的必要性。实质证据表明,影响囊肿发育的信号通路成分(例如cAMP,细胞内钙,受体酪氨酸激酶,瞬时受体电位阳离子通道亚族V成员4(TRPV4)通道,雷帕霉素的机械靶标(mTOR))的实验操作,组蛋白脱乙酰酶(HDAC6),Cdc25A磷酸酶,miRNAs和金属蛋白酶)减弱肝囊肿的生长。许多这些靶点已经在临床前临床试验中进行了评估,表明其作为潜在的新疗法的价值。本综述概述了目前PLD的临床和临床前治疗策略。
关键词: 胆管细胞,胆管癌,纤毛,肝囊肿,多囊肝病,治疗
图形摘要
Current Drug Targets
Title:Therapeutic Targets in Polycystic Liver Disease
Volume: 18 Issue: 8
关键词: 胆管细胞,胆管癌,纤毛,肝囊肿,多囊肝病,治疗
摘要: Polycystic liver diseases (PLD) are a group of genetic disorders initiated by mutations in several PLD-related genes and characterized by the presence of multiple cholangiocyte-derived hepatic cysts that progressively replace liver tissue. PLD co-exists with Autosomal Dominant Polycystic Kidney Disease (ADPKD) and Autosomal Recessive PKD as well as occurs alone (i.e., Autosomal Dominant Polycystic Liver Disease [ADPLD]). PLD associated with ADPKD and ARPKD belong to a group of disorders known as cholangiociliopathies since many disease-causative and disease-related proteins are expressed in primary cilia of cholangiocytes. Aberrant expression of these proteins in primary cilia affects their structures and functions promoting cystogenesis. Current medical therapies for PLD include symptomatic management and surgical interventions. To date, the only available drug treatment for PLD patients that halt disease progression and improve quality of life are somatostatin analogs. However, the modest clinical benefits, need for long-term maintenance therapy, and the high cost of treatment justify the necessity for more effective treatment options. Substantial evidence suggests that experimental manipulations with components of the signaling pathways that influence cyst development (e.g., cAMP, intracellular calcium, receptor tyrosine kinase, transient receptor potential cation channel subfamily V member 4 (TRPV4) channel, mechanistic target of rapamycin (mTOR), histone deacetylase (HDAC6), Cdc25A phosphatase, miRNAs and metalloproteinases) attenuate growth of hepatic cysts. Many of these targets have been evaluated in pre-clinical trials suggesting their value as potential new therapies. This review outlines the current clinical and preclinical treatment strategies for PLD.
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Cite this article as:
Therapeutic Targets in Polycystic Liver Disease, Current Drug Targets 2017; 18 (8) . https://dx.doi.org/10.2174/1389450116666150427161743
DOI https://dx.doi.org/10.2174/1389450116666150427161743 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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