VIP17/MAL expression modulates epithelial cyst formation and ciliogenesis.
VIP17/MAL expression modulates epithelial cyst formation and ciliogenesis.
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VIP17/MAL 表达调节上皮囊肿形成和纤毛发生。
DOI：
10.1152/ajpcell.00338.2011
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发表时间：
2012
期刊：
影响因子：
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通讯作者：
Caplan,MichaelJ
中科院分区：
文献类型：
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作者：
Takiar,Vinita;Mistry,Kavita;Carmosino,Monica;Schaeren-Wiemers,Nicole;Caplan,MichaelJ
上皮细胞的极化组织是矢量溶质转运所必需的，并且可能在肾囊性疾病中发生改变。 17 kDa 的囊泡整合蛋白 (VIP17/MAL) 参与顶囊泡运输。 VIP17/MAL 体内过度表达导致病因不明的肾囊肿发生。肾囊肿发生可能是初级纤毛缺陷的结果。为了探讨 VIP17/MAL 在肾囊肿发生和纤毛发生中的作用，我们检测了在二维 (2D) 和三维 (3D) 囊肿培养中生长的野生型和 VIP17/MAL 过表达 Madin-Darby 犬肾肾上皮细胞的极化和纤毛形态。当在 2D 和 3D 培养物中维持的细胞中表达时，VIP17/MAL 位于顶部。与对照组相比，VIP17/MAL 过表达细胞产生更多的多腔囊肿。虽然基底外侧标记的分布不受影响，但 VIP17/MAL 表达导致顶端标记 gp135 到初级纤毛的异常排序。 VIP17/MAL 过度表达也与纤毛缩短或缺失有关。对 VIP17/MAL 转基因小鼠肾脏切片进行的免疫荧光分析也表明，扩张管腔内的纤毛较少且缩短（P < 0.01）。这些研究表明，VIP17/MAL 过表达会导致体外和体内纤毛和囊肿发育异常，这表明 VIP17/MAL 过表达小鼠可能会继发于纤毛缺陷而形成囊肿。
The polarized organization of epithelial cells is required for vectorial solute transport and may be altered in renal cystic diseases. Vesicle integral protein of 17 kDa (VIP17/MAL) is involved in apical vesicle transport. VIP17/MAL overexpression in vivo results in renal cystogenesis of unknown etiology. Renal cystogenesis can occur as a consequence of defects of the primary cilium. To explore the role of VIP17/MAL in renal cystogenesis and ciliogenesis, we examined the polarization and ciliary morphology of wild-type and VIP17/MAL overexpressing Madin-Darby canine kidney renal epithelial cells grown in two-dimensional (2D) and three-dimensional (3D) cyst culture. VIP17/MAL is apically localized when expressed in cells maintained in 2D and 3D culture. VIP17/MAL overexpressing cells produce more multilumen cysts compared with controls. While the distributions of basolateral markers are not affected, VIP17/MAL expression results in aberrant sorting of the apical marker gp135 to the primary cilium. VIP17/MAL overexpression is also associated with shortened or absent cilia. Immunofluorescence analysis performed on kidney sections from VIP17/MAL transgenic mice also demonstrates fewer and shortened cilia within dilated lumens (P< 0.01). These studies demonstrate that VIP17/MAL overexpression results in abnormal cilium and cyst development, in vitro and in vivo, suggesting that VIP17/MAL overexpressing mice may develop cysts secondary to a ciliary defect.