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.