Masyuk Tatyana, Masyuk Anatoliy, LaRusso Nicholas
Miles and Shirley Fiterman Center for Digestive Diseases, Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.
Curr Opin Gastroenterol. 2009 May;25(3):265-71. doi: 10.1097/MOG.0b013e328328f4ff.
The present review summarizes recent knowledge on polycystic liver diseases (PCLDs), mechanisms of hepatic cystogenesis and potential therapies for these conditions.
PCLD may be classified as cholangiociliopathies. In PCLD associated with polycystic kidney disease, cell proliferation is one of the major mechanisms of cystogenesis, whereas in isolated PCLD (autosomal dominant polycystic liver disease), disrupted cell adhesion may be more important in cyst progression. In cystic cholangiocytes, overexpression of ion transporters and water channels facilitates fluid secretion into the cystic lumen, and growth factors, estrogens and cytokines promote cholangiocyte proliferation. With age, cholangiocytes lining liver cysts acquire features of mesenchymal cells contributing to hepatic fibrocystogenesis. A novel mechanism of liver cyst expansion in PCLD involves microRNA regulatory pathways. Hyperproliferation of cystic cholangiocytes is linked to abnormalities in cell cycle progression and microRNA expression. Decreased levels of miR-15a are coupled to upregulation of its target--the cell cycle regulator, Cdc25A. Cholangiocyte cilia in liver cysts are structurally abnormal. Somatostatin analogues and sirolimus reduce liver cyst volume in PCLD patients.
Clarification of molecular mechanisms of hepatic cystogenesis provides an opportunity for the development of targeted therapeutic options in PCLD.
本综述总结了关于多囊肝病（PCLDs）、肝囊肿发生机制以及这些病症潜在治疗方法的最新知识。
PCLD可归类为胆管纤毛病。在与多囊肾病相关的PCLD中，细胞增殖是囊肿发生的主要机制之一，而在孤立性PCLD（常染色体显性多囊肝病）中，细胞黏附破坏在囊肿进展中可能更为重要。在囊性胆管细胞中，离子转运体和水通道的过度表达促进液体分泌到囊腔内，生长因子、雌激素和细胞因子促进胆管细胞增殖。随着年龄增长，肝囊肿内衬的胆管细胞获得间充质细胞特征，促进肝纤维囊肿形成。PCLD中肝囊肿扩张的一种新机制涉及微小RNA调控途径。囊性胆管细胞的过度增殖与细胞周期进程和微小RNA表达异常有关。miR-15a水平降低与其靶标——细胞周期调节因子Cdc25A的上调相关。肝囊肿中的胆管细胞纤毛结构异常。生长抑素类似物和西罗莫司可减小PCLD患者的肝囊肿体积。
肝囊肿发生分子机制的阐明为PCLD中靶向治疗方案的开发提供了机会。
