Renal cilia display length alterations following tubular injury and are present early in epithelial repair
Renal cilia display length alterations following tubular injury and are present early in epithelial repair
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DOI：
10.1093/ndt/gfm743
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发表时间：
2008-03-01
影响因子：
6.1
通讯作者：
Deane, James A.
中科院分区：
文献类型：
--
作者：
Verghese, Elizabeth;Weidenfeld, Raphael;Deane, James A.
背景肾纤毛是维持正常肾脏结构所需的流量传感器。这种细胞器的缺陷经常与多囊肾疾病有关，但肾纤毛在急性肾小管损伤中的作用尚未研究。我们分析了肾缺血-再灌注和输尿管梗阻损伤后小鼠肾纤毛的存在和尺寸，并将这些结果与肾小管的损伤和修复相关。检测缺血再灌注损伤后编码纤毛定位蛋白基因的表达。缺血再灌注损伤被证明影响肾小管和导管中纤毛的长度。与对照未损伤的近端小管（4.2 +/- 0.3 μ m）相比，损伤后1天（2.8 +/- 0.4 μ m）和2天（3.0 +/-0.2 μ m）近端小管中肾纤毛的平均长度减少。随后在4天和7天的损伤和修复过程中，近端小管/集合管（7天= 6.2 +/- 0.3 μ m）和远端小管/集合管（4天= 4.4 +/- 0.3 μ m; 7天= 5.5 +/- 0.4 μ m;对照组2.5 +/- 0.1 μ m）中纤毛的平均长度增加。编码纤毛定位产物的基因的表达水平与缺血再灌注损伤后纤毛长度的增加无关。输尿管梗阻8天也导致远端小管/集合管中肾纤毛延长（8天UUO = 5.8 +/- 0.3 μ m;对照组2.5 +/- 0.1 μ m）。在缺血-再灌注损伤后的修复过程中，去分化细胞上存在纤毛，这些细胞增殖并具有上皮表型，以促进缺血性肾小管的修复。我们提出了肾纤毛在响应损伤引起的肾环境变化中的作用，以及在重建受损肾小管上皮层的修复过程中的作用。
Background. Renal cilia are flow sensors that are required for the maintenance of normal kidney architecture. Defects in this organelle are frequently associated with polycystic kidney disease, but the role of renal cilia during acute tubular injury has not been investigated.Methods. We have analysed the presence and dimensions of renal cilia following renal ischaemia-reperfusion and ureteral obstruction injury in the mouse, and related these results to injury and repair of the renal tubule. The expression of genes encoding cilium-localized proteins was measured following ischaemia-reperfusion injury.Results. Ischaemia-reperfusion injury was demonstrated to affect the length of cilia in the renal tubule and duct. The average length of renal cilia in the proximal tubule decreases 1 day (2.8 +/- 0.4 mu m) and 2 days (3.0 +/- 0.2 mu m) after injury, as compared to the control uninjured proximal tubule (4.2 +/- 0.3 mu m). Later in the injury and repair process at 4 and 7 days, the average length of cilia increases in both the proximal (7 days = 6.2 +/- 0.3 mu m) and distal tubule/collecting duct (4 days = 4.4 +/- 0.3 mu m; 7 days = 5.5 +/- 0.4 mu m; control 2.5 +/- 0.1 mu m). The expression level of genes encoding cilium-localized products did not correlate with the increase in cilium length following ischaemia-reperfusion injury. Ureteral obstruction for 8 days also caused lengthening (8 days UUO = 5.8 +/- 0.3 mu m; control 2.5 +/- 0.1 mu m) of renal cilia in the distal tubule/collecting duct. During the repair process that follows ischaemia-reperfusion injury, cilia were present on the dedifferentiated cells that proliferate and adopt an epithelial phenotype to facilitate the repair of the ischaemic renal tubule.Conclusions. We propose roles for the renal cilium in responding to changes in the renal environment caused by injury, and in the repair process that re-establishes the epithelial layer of the damaged renal tubule.