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Modelling distal convoluted tubule (patho)physiology
Tissue Engineering, Part C: Methods ( IF 2.7 ) Pub Date : 2021-02-05
Miss Charlotte J.A. Olde Hanhof, Mr. Fjodor A Yousef Yengej, Dr. Maarten B Rookmaaker, Dr. Marianne C Verhaar, Dr. Jenny Van der Wijst, Dr. Joost G Hoenderop

The kidneys are essential for maintaining electrolyte homeostasis. Blood electrolyte composition is controlled by active reabsorption and secretion processes in dedicated segments of the kidney tubule. Specifically, the distal convoluted tubule (DCT) and connecting tubule are important for regulating the final excretion of sodium, magnesium, and calcium. Studies unravelling the specific function of these segments have greatly improved our understanding of DCT (patho)physiology. Over the years, experimental models used to study the DCT have changed and the field has advanced from early dissection studies with rats and rabbits to the use of various transgenic mouse models. Developments in dissection techniques and cell culture methods have resulted in immortalized mouse DCT cell lines and made it possible to specifically obtain DCT fragments for <i>ex vivo </i>studies. However, we still do not fully understand the complex (patho)physiology of this segment and there is need for advanced human DCT models. Recently, kidney organoids and tubuloids have emerged as new complex cell models that provide excellent opportunities for physiological studies, disease modelling, drug discovery, and even personalized medicine in the future. This review presents an overview of cell models used to study the DCT and provides an outlook on kidney organoids and tubuloids as model for DCT (patho)physiology.

中文翻译:

模拟远曲弯小管(病理)生理

肾脏对于维持电解质稳态至关重要。血液电解质的成分是通过肾小管特定部位的主动重吸收和分泌过程来控制的。具体而言,远曲小管(DCT)和连接小管对于调节钠,镁和钙的最终排泄至关重要。揭示这些部分具体功能的研究极大地提高了我们对DCT(病理)生理学的理解。多年来,用于研究DCT的实验模型已经发生了变化,并且该领域已经从对大鼠和兔子的早期解剖研究发展为使用各种转基因小鼠模型。解剖技术和细胞培养方法的发展已产生了永生的小鼠DCT细胞系,并有可能特异性地获得用于 i>离体研究</ i>研究。但是,我们仍然不完全了解这一部分的复杂(病理)生理学,因此需要先进的人类DCT模型。近年来,肾脏类器官和类微管已经出现,成为新的复杂细胞模型,为将来的生理学研究,疾病建模,药物发现乃至个性化医学提供了绝佳的机会。这项审查提供了用于研究DCT的细胞模型的概述,并提供了肾脏类器官和肾小管作为DCT(病理)生理学模型的前景。肾脏类器官和肾小管已经作为新的复杂细胞模型出现,为将来的生理学研究,疾病建模,药物发现乃至个性化医学提供了极好的机会。这项审查提供了用于研究DCT的细胞模型的概述,并提供了肾脏类器官和肾小管作为DCT(病理)生理学模型的前景。肾脏类器官和肾小管已经作为新的复杂细胞模型出现,为将来的生理学研究,疾病建模,药物发现乃至个性化医学提供了极好的机会。这项审查提供了用于研究DCT的细胞模型的概述,并提供了肾脏类器官和肾小管作为DCT(病理)生理学模型的前景。
更新日期:2021-02-05
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