Dept. of Cellular Biology and Anatomy, Medical College of Georgia, Augusta, GA 30912.
Am J Physiol Renal Physiol. 2013 Oct 15;305(8):F1085-98. doi: 10.1152/ajprenal.00399.2013. Epub 2013 Jul 31.
Cilia, membrane-enclosed organelles protruding from the apical side of cells, can be divided into two classes: motile and primary cilia. During the past decades, motile cilia have been intensively studied. However, it was not until the 1990s that people began to realize the importance of primary cilia as cellular-specific sensors, particularly in kidney tubular epithelial cells. Furthermore, accumulating evidence indicates that primary cilia may be involved in the regulation of cell proliferation, differentiation, apoptosis, and planar cell polarity. Many signaling pathways, such as Wnt, Notch, Hedgehog, and mammalian target of rapamycin, have been located to the primary cilia. Thus primary cilia have been regarded as a hub that integrates signals from the extracellular environment. More importantly, dysfunction of this organelle may contribute to the pathogenesis of a large spectrum of human genetic diseases, named ciliopathies. The significance of primary cilia in acquired human diseases such as hypertension and diabetes has gradually drawn attention. Interestingly, recent reports disclosed that cilia length varies during kidney injury, and shortening of cilia enhances the sensitivity of epithelial cells to injury cues. This review briefly summarizes the current status of cilia research and explores the potential mechanisms of cilia-length changes during kidney injury as well as provides some thoughts to allure more insightful ideas and promotes the further study of primary cilia in the context of kidney injury.
纤毛是一种从细胞顶部伸出的膜包裹细胞器,可以分为两类:运动纤毛和初级纤毛。在过去的几十年中,人们对运动纤毛进行了深入研究。然而,直到 20 世纪 90 年代,人们才开始意识到初级纤毛作为细胞特异性传感器的重要性,尤其是在肾小管上皮细胞中。此外,越来越多的证据表明,初级纤毛可能参与细胞增殖、分化、凋亡和平面细胞极性的调节。许多信号通路,如 Wnt、Notch、Hedgehog 和哺乳动物雷帕霉素靶蛋白,已被定位到初级纤毛。因此,初级纤毛被认为是整合来自细胞外环境信号的中心。更重要的是,该细胞器的功能障碍可能导致一大类人类遗传疾病的发病机制,这些疾病被称为纤毛病。初级纤毛在高血压和糖尿病等获得性人类疾病中的重要性逐渐引起了关注。有趣的是,最近的报道揭示了肾脏损伤过程中纤毛长度的变化,并且纤毛缩短增强了上皮细胞对损伤信号的敏感性。本文简要总结了纤毛研究的现状,探讨了肾脏损伤过程中纤毛长度变化的潜在机制,并提供了一些思路,以吸引更有见地的想法,促进在肾脏损伤背景下对初级纤毛的进一步研究。