Glycogen synthase kinase-3 regulation of urinary concentrating ability.
OBJECTIVE
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.


RESULTS
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.


CONCLUSIONS
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.
The Kidney Institute, Department of Medicine, University of Kansas Medical Center, Kansas City, Kansas 66160, USA. rrao@kumc.edu
Reena
R
Rao
D000818:Animals; D051399:Aquaporin 2 / Q000378:metabolism; D001692:Biological Transport; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D006801:Humans; D007685:Kidney Tubules, Collecting / Q000201:enzymology*; D015398:Signal Transduction; D014667:Vasopressins / Q000378:metabolism
D051399:Aquaporin 2; D014667:Vasopressins; D038362:Glycogen Synthase Kinase 3