Ganner Athina, Neumann-Haefelin Elke
Department of Nephrology, Medical Center, University of Freiburg, Hugstetter Strasse 55, 79106 Freiburg, Germany.
Cell Tissue Res. 2017 Jul;369(1):105-118. doi: 10.1007/s00441-017-2622-z. Epub 2017 May 8.
Despite its apparent simplicity, the nematode Caenorhabditis elegans has a high rating as a model in molecular and developmental biology and biomedical research. C. elegans has no excretory system comparable with the mammalian kidney but many of the genes and molecular pathways involved in human kidney diseases are conserved in C. elegans. The plethora of genetic, molecular and imaging tools available in C. elegans has enabled major discoveries in renal research and advanced our understanding of the pathogenesis of genetic kidney diseases. In particular, studies in C. elegans have pioneered the fundamental role of cilia for cystic kidney diseases. In addition, proteins of the glomerular filtration barrier and podocytes are critical for cell recognition, assembly of functional neuronal circuits, mechanosensation and signal transduction in C. elegans. C. elegans has also proved tremendously valuable for aging research and the Von Hippel-Lindau tumor suppressor gene has been shown to modulate lifespan in the nematode. Further, studies of the excretory canal, membrane transport and ion channel function in C. elegans have provided insights into mechanisms of tubulogenesis and cellular homeostasis. This review recounts the way that C. elegans can be used to investigate various aspects of genetic and molecular nephrology. This model system opens up an exciting and new area of study of renal development and diseases.
尽管线虫秀丽隐杆线虫看似简单，但在分子与发育生物学以及生物医学研究中，它作为一种模型具有很高的价值。秀丽隐杆线虫没有与哺乳动物肾脏相当的排泄系统，但许多参与人类肾脏疾病的基因和分子途径在秀丽隐杆线虫中是保守的。秀丽隐杆线虫拥有大量的遗传、分子和成像工具，这使得在肾脏研究中取得了重大发现，并加深了我们对遗传性肾脏疾病发病机制的理解。特别是，对秀丽隐杆线虫的研究开创了纤毛在多囊肾病中基础作用的先河。此外，肾小球滤过屏障和足细胞的蛋白质对于秀丽隐杆线虫中的细胞识别、功能性神经回路的组装、机械感觉和信号转导至关重要。秀丽隐杆线虫在衰老研究中也被证明具有巨大价值，并且已表明冯·希佩尔-林道肿瘤抑制基因可调节线虫的寿命。此外，对秀丽隐杆线虫排泄管、膜转运和离子通道功能的研究为肾小管发生和细胞稳态机制提供了见解。这篇综述讲述了秀丽隐杆线虫可用于研究遗传和分子肾脏病学各个方面的方式。这个模型系统开辟了一个关于肾脏发育和疾病的令人兴奋的新研究领域。
