The cellular response to osmotic stress ensures that the concentration of
water inside the cell is maintained within a range that is compatible
with biologic function. Single cell organisms are particularly dependent
on mechanisms that permit adaptation to osmotic stress because each
individual cell is directly exposed to the external environment. Mammals,
however, limit osmotic stress by establishing an internal aqueous
environment in which intravascular water and electrolytes are subject to
sensitive and dynamic, organism-based homeostatic regulation.
NFAT5/TonEBP is an essential mammalian osmoregulatory transcription
factor, and this invention demonstrates the unexpected yet critical
significance of cell-based osmotic regulation in vivo. The invention
highlights the fundamental importance of maintaining intracellular water
homeostasis in the face of varying cellular metabolic activity and
distinct tissue microenvironments. Methods for treating, preventing, or
inhibiting human diseases using the osmotic stress pathway have been
provided.