In vivo and in vitro osmotic regulation of HSP-70 and prostaglandin synthase gene expression in kidney cells

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 that may be important in adaptation of renal medullary cells to hyperosmolality. We demonstrate selective, modulated expression in the renal medulla of heat shock protein HSP-70 mRNA and prostaglandin synthase-l 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. HSP-70 and prostaglandin synthase-2 mRNA levels increased when extracellular osmolality was increased to 400-600 mosmol/kg by the addition of NaCl. At 500 mosmol/kg this response was evident at 6 h, was maximal near 24 h, and persisted for a total of 90 days. Prostaglandin synthase-l 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 HSP-70 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 HSP-70 and prostaglandin synthase-l 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.