In vivo and in vitro osmotic regulation of hsp70 and prostaglandin synthase gene expression in kidney cells. Cowley, Benjamin D., Jr, Michelle J. Muessel, David Douglass, and William Wilkins. Departments of Medicine and Biochemistry & Molecular Biology, University of Kansas Medical Center, Kansas City, KS 66160-7405
APStracts 2:0119F, 1995.
As a function of the urinary concentrating mechanism, the cells of the renal medulla are exposed to elevated and constantly varying osmolalities and adapt to this environment by selectively expressing certain mRNAs. We evaluated the expression and regulation of two RNAs which may be important in adaptation of renal medullary cells to hyperosmolality. We demonstrate selective, modulated expression in the renal medulla of heat shock protein Hsp70 mRNA and prostaglandin synthase-1 mRNA, with the abundance of these two mRNAs regulated in vivo in concert with changes in medullary sodium and urea. We also determined the abundance of these mRNAs in cultured kidney cells (MDCK) in response to an increase in extracellular osmolality due to selected osmotic agents. Hsp70 and prostaglandin synthase-2 mRNA levels increased when extracellular osmolality was increased to 400 - 600 mOsm/kg by the addition of NaCl. At 500 mOsm/kg this response was evident at 6 h, was maximal near 24 h, and persisted for a total of 90 days. Prostaglandin synthase-1 mRNA levels in MDCK cells were also increased after chronic exposure to extracellular osmolality. Increased extracellular osmolality caused by agents to which cells are impermeable caused increased levels of Hsp70 and prostaglandin synthase-2 mRNAs, whereas increased extracellular osmolality caused by agents to which cells are permeable did not; thus osmotic regulation involved osmotic water movement. We conclude that the abundance of Hsp70 and prostaglandin synthase-1 mRNAs in the renal medulla is regulated in response to renal medullary osmolality and suggest that this may also be true for other medullary mRNAs yet to be described.

Received 2 July 1993; accepted in final form 1 July 1995.
APS Manuscript Number F224-3.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 18 July 1995.