Unilateral nephrectomy elongates primary cilia in the remaining kidney via reactive oxygen species.
Unilateral nephrectomy elongates primary cilia in the remaining kidney via reactive oxygen species.
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DOI：
10.1038/srep22281
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发表时间：
2016-02-29
影响因子：
4.6
通讯作者：
Park KM
中科院分区：
文献类型：
--
作者：
Han SJ;Jang HS;Kim JI;Lipschutz JH;Park KM
初级纤毛的长度与正常细胞和器官功能相关。在肾脏中，功能性纤毛长度/质量的变化与缺血/再灌注损伤、多囊肾、先天性孤立肾等多种疾病有关。在这里，我们研究肾脏质量减少是否影响初级纤毛长度和功能。为了减少肾脏质量，对小鼠进行单侧肾切除术（UNx）。 UNx 增加了肾脏重量和剩余肾脏中超氧化物的形成。剩余肾脏的近端肾小管细胞、集合管细胞和壁细胞中的初级纤毛被拉长。 Mn(III) 四（1-甲基-4-吡啶基）卟啉 (MnTMPyP) 是一种抗氧化剂，可减少 UNx 小鼠中超氧化物的形成，并阻止初级纤毛的伸长。 UNx 增加了剩余肾脏中磷酸化 ERK、p21 以及外囊复合体成员 Sec8 和 Sec10 的表达，并且这些增加被 MnTMPyP 阻止。在MDCK（一种肾小管上皮细胞系）中，低浓度H2O2处理的细胞初级纤毛伸长。 MnTMPyP 处理也可以阻止 H2O2 诱导的初级纤毛伸长。总而言之，这些数据表明，由肾脏质量减少引起的肾脏补偿会导致初级纤毛伸长，并且这种伸长与活性氧（ROS）产生的增加有关。
The length of primary cilia is associated with normal cell and organ function. In the kidney, the change of functional cilia length/mass is associated with various diseases such as ischemia/reperfusion injury, polycystic kidney disease, and congenital solitary kidney. Here, we investigate whether renal mass reduction affects primary cilia length and function. To induce renal mass reduction, mice were subjected to unilateral nephrectomy (UNx). UNx increased kidney weight and superoxide formation in the remaining kidney. Primary cilia were elongated in proximal tubule cells, collecting duct cells and parietal cells of the remaining kidney. Mn(III) Tetrakis (1-methyl-4-pyridyl) porphyrin (MnTMPyP), an antioxidant, reduced superoxide formation in UNx-mice and prevented the elongation of primary cilia. UNx increased the expression of phosphorylated ERK, p21, and exocyst complex members Sec8 and Sec10, in the remaining kidney, and these increases were prevented by MnTMPyP. In MDCK, a kidney tubular epithelial cell line, cells, low concentrations of H2O2 treatment elongated primary cilia. This H2O2-induced elongation of primary cilia was also prevented by MnTMPyP treatment. Taken together, these data demonstrate that kidney compensation, induced by a reduction of renal mass, results in primary cilia elongation, and this elongation is associated with an increased production of reactive oxygen species (ROS).