Ciliotherapy: a novel intervention in polycystic kidney disease
Ciliotherapy: a novel intervention in polycystic kidney disease
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DOI：
10.3969/j.issn.1671-5411.2014.01.001
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发表时间：
2014-01-01
影响因子：
2.5
通讯作者：
Nauli, Surya M.
中科院分区：
文献类型：
--
作者：
Kathem, Sarmed H.;Mohieldin, Ashraf M.;Nauli, Surya M.
背景纤毛病是一组与初级纤毛结构或功能异常有关的疾病。纤毛病包括多囊肾病（PKD），一种与血管性高血压相关的病理学。我们以前表明，纤毛长度调节纤毛功能，纤毛功能是内皮细胞一氧化氮（NO）生物合成所必需的。由于PKD患者表现出异常的感觉纤毛功能，我们目前的研究的目的是寻找一种有针对性的治疗集中在初级纤毛，我们称之为ciliotherapy.Methods和结果在目前的研究中，我们在体外分析精制非诺多泮作为一个等效的和更具体的多巴胺能激动剂来调节纤毛长度和功能。我们的体内研究表明，在PKD小鼠模型中，非诺多泮增加纤毛长度和血清NO，从而降低血压。我们的交叉，多中心，双盲和安慰剂对照的临床研究进一步表明，纤毛靶向治疗显示了整体平均动脉压降低PKD patient.Conclusions总体而言，我们的研究提供了第一个证据ciliotherapy作为一种创新的干预异常初级纤毛的患者。
Background Ciliopathies are a group of diseases associated with abnormal structure or function of primary cilia. Ciliopathies include polycystic kidney disease (PKD), a pathology associated with vascular hypertension. We previously showed that cilia length regulates cilia function, and cilia function is required for nitric oxide (NO) biosynthesis in endothelial cells. Because patients with PKD show abnormal sensory cilia function, the aim of our current study was to search for a targeted therapy focused on primary cilia, which we refer to as 'ciliotherapy'.Methods and Results In the present studies, our in vitro analyses refined fenoldopam as an equipotent and more specific dopaminergic agonist to regulate cilia length and function. Our in vivo studies indicated that fenoldopam increased cilia length and serum NO thereby reducing blood pressure in a PKD mouse model. Our crossover, multicenter, double-blind and placebo-controlled clinical study further indicated that cilia-targeting therapy showed an overall reduction in mean arterial pressure in PKD patients.Conclusions Overall, our studies provide the first evidence of ciliotherapy as an innovative intervention in patients with abnormal primary cilia.