Multiple Primary Cilia Modulate the Fluid Transcytosis in Choroid Plexus Epithelium
Multiple Primary Cilia Modulate the Fluid Transcytosis in Choroid Plexus Epithelium
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DOI：
10.1111/j.1600-0854.2009.01016.x
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发表时间：
2010-02-01
期刊：
影响因子：
4.5
通讯作者：
Takeda, Sen
中科院分区：
文献类型：
--
作者：
Narita, Keishi;Kawate, Toyoko;Takeda, Sen
纤毛的功能缺陷与包括先天性脑积水在内的各种人类疾病有关。以往的研究表明，纤毛的缺陷不仅破坏了由室管膜中的运动纤毛产生的脑脊液（CSF）的流动，而且还导致脉络丛中CSF的产生增加。然而，睫状体功能障碍导致CSF过量产生的分子机制仍然难以捉摸。为探讨其分子机制，从猪脑中分离脉络丛上皮细胞。这些细胞在顶端表面表达初级纤毛簇。CPECs的脱落提高了细胞内环腺苷酸（cAMP）水平，刺激基底外侧至顶端的液体转胞吞，而不会对其他形态和生理特征产生不利影响。初级纤毛具有神经肽FF（NPFF）受体2。在去纤毛细胞中，在纳摩尔浓度下对NPFF的反应性降低。此外，CPEC表达NPFF前体沿着NPFFR 2。NPFFR拮抗剂BIBP3226增加了液体转胞吞作用，表明CPEC中存在自分泌NPFF信号传导，对液体转胞吞作用具有紧张性抑制作用。这些结果表明，初级纤毛在CPECs的集群作为一个敏感的化学传感器，以调节CSF的生产。
Functional defects in cilia are associated with various human diseases including congenital hydrocephalus. Previous studies suggested that defects in cilia not only disrupt the flow of cerebrospinal fluid (CSF) generated by motile cilia in ependyma lining the brain ventricles, but also cause increased CSF production at the choroid plexus. However, the molecular mechanisms of CSF overproduction by ciliary dysfunction remain elusive. To dissect the molecular mechanisms, choroid plexus epithelial cells (CPECs) were isolated from porcine brain. These cells expressed clusters of primary cilia on the apical surface. Deciliation of CPECs elevated the intracellular cyclic AMP (cAMP) levels and stimulated basolateral-to-apical fluid transcytosis, without detrimental effects on other morphological and physiological features. The primary cilia possessed neuropeptide FF (NPFF) receptor 2. In deciliated cells, the responsiveness to NPFF was reduced at nanomolar concentrations. Furthermore, CPECs expressed NPFF precursor along with NPFFR2. An NPFFR antagonist, BIBP3226, increased the fluid transcytosis, suggesting the presence of autocrine NPFF signaling in CPECs for a tonic inhibition of fluid transcytosis. These results suggest that the clusters of primary cilia in CPECs act as a sensitive chemosensor to regulate CSF production.