Monash Immunology and Stem Cell Laboratories, Monash University, Melbourne, Victoria, Australia.
Cell Biol Int. 2011 Sep;35(9):909-13. doi: 10.1042/CBI20090154.
Primary cilia are non-motile sensory organelles that project from cells in many tissues. The role of renal primary cilium-based signalling in regulating epithelial cell proliferation and differentiation is highlighted by studies showing that defects of the cilium lead to epithelial de-differentiation, over proliferation and polycystic kidney disease. Recent studies show that renal primary cilia may also play a role in controlling epithelial differentiation during renal repair. After injury, renal cilium length increases dramatically and then undergoes a normalization that coincides with structural and functional repair in both human patients and mouse models of renal injury. These changes in cilium length are likely to modulate cilium-based signalling, but the injury-related factors that influence renal primary cilium length have yet to be determined. Here, we investigated the effect of three factors commonly associated with renal injury on renal cilium length in an in vitro setting. MDCK (Madin Darby canine kidney) cell cultures bearing primary cilia were treated with BSA to simulate albuminuria, cobalt chloride to simulate hypoxia and the inflammation-related cytokine tumour necrosis factor α. Primary cilium length was only increased in cultures treated with cobalt chloride. Our results suggest a role for hypoxia and the induction of HIF-1α (hypoxia-inducible factor 1α) in increasing renal primary cilium length following renal injury.
原发性纤毛是从许多组织的细胞中伸出的非运动感觉细胞器。研究表明，纤毛缺陷会导致上皮细胞去分化、过度增殖和多囊肾病，这凸显了肾脏原发性纤毛信号在调节上皮细胞增殖和分化中的作用。最近的研究表明，肾脏原发性纤毛在肾脏修复过程中也可能在控制上皮细胞分化中发挥作用。损伤后，肾脏纤毛长度显著增加，然后纤毛长度恢复正常，这与人类患者和肾脏损伤的小鼠模型的结构和功能修复相吻合。纤毛长度的这些变化可能调节基于纤毛的信号，但影响肾脏原发性纤毛长度的损伤相关因素尚未确定。在这里，我们在体外环境中研究了三种通常与肾脏损伤相关的因素对肾脏纤毛长度的影响。用 BSA 处理携带原发性纤毛的 MDCK（Madin Darby 犬肾）细胞培养物，模拟白蛋白尿，用氯化钴模拟缺氧，用炎症相关细胞因子肿瘤坏死因子 α 处理。只有在用钴处理的培养物中，原发性纤毛长度才会增加。我们的结果表明，缺氧和诱导 HIF-1α（缺氧诱导因子 1α）在肾脏损伤后增加肾脏原发性纤毛长度中起作用。
