The Kidney Institute, Department of Medicine, University of Kansas Medical Center, Kansas City, Kansas 66160, USA.
Curr Opin Nephrol Hypertens. 2012 Sep;21(5):541-6. doi: 10.1097/MNH.0b013e32835571d4.
Glycogen synthase kinase-3 (GSK3) is an enzyme that is gaining prominence as a critical signaling molecule in the epithelial cells of renal tubules. This review will focus on recent findings exploring the role of GSK3 in renal collecting ducts, especially its role in urine concentration involving vasopressin signaling.
Recent studies using inhibition or tissue-specific gene deletion of GSK3 revealed the mechanism by which GSK3 regulates aquaporin 2 water channels via adenylate cyclase or the prostaglandin-E2 pathway. In other studies, postnatal treatment with lithium, an inhibitor of GSK3, increased cell proliferation and led to microcyst formation in rat kidneys. These studies suggest that loss of GSK3 activity could interfere with renal water transport at two levels. In the short term, it could disrupt vasopressin signaling in collecting duct cells and in the long term it could alter the structure of the collecting ducts, making them less responsive to the hydro-osmotic effects of vasopressin.
Ongoing studies reveal the crucial role played by GSK3 in the regulation of vasopressin action in the renal collecting ducts and suggest a possible use of GSK3 inhibitors in disease conditions associated with disrupted vasopressin signaling.
糖原合成酶激酶 3（GSK3）是一种酶，作为肾小管上皮细胞中关键的信号分子而受到越来越多的关注。本综述将重点介绍最近探索 GSK3 在肾集合管中作用的研究发现，特别是其在涉及血管加压素信号的尿液浓缩中的作用。
最近的研究使用 GSK3 的抑制或组织特异性基因缺失，揭示了 GSK3 通过腺苷酸环化酶或前列腺素 E2 途径调节水通道蛋白 2（AQP2）水通道的机制。在其他研究中，出生后用 GSK3 的抑制剂锂处理增加了大鼠肾脏中的细胞增殖，并导致微囊形成。这些研究表明，GSK3 活性的丧失可能在两个水平上干扰肾脏水转运。短期内，它可能破坏集合管细胞中的血管加压素信号，长期来看，它可能改变集合管的结构，使它们对血管加压素的水渗透作用反应迟钝。
正在进行的研究揭示了 GSK3 在调节肾集合管中血管加压素作用中的关键作用，并提示可能在与血管加压素信号中断相关的疾病状态下使用 GSK3 抑制剂。
