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Articles in PresS, published online ahead of print September 5, 2001
Am J Physiol Cell Physiol, 10.1152/ajpcell.00267.2001
Submitted on June 15, 2001
Accepted on August 24, 2001
1 Medicine, Johns Hopkins University, Baltimore, Maryland, USA
* To whom correspondence should be addressed. E-mail: mkwon{at}jhmi.edu.
Osmolality of the mammalian renal medulla is high due to the operation of urinary concentrating mechanism. To understand molecular events during the early phase of cellular adaptation to hypertonicity, we performed comprehensive searches for genes induced in response to hypertonicity using a cell line (mIMCD3) derived from inner medullary collecting duct of mouse kidney. PCR-based subtractive hybridization of cDNA pools and cDNA microarray analysis were used. We report 12 genes whose mRNA expression is significantly increased within 4 hours after exposure to hypertonicity. The increase in mRNA expression was due to increased transcription. Many are either stress response genes or growth regulatory genes, supporting the notion that hypertonicitiy evokes stress response and growth regulation in cells. Experiments using inhibitors revealed that mitogen-activated protein kinases were commonly involved in signaling for the induction of genes by hypertonicity. Tyrosine kinases and phosphatidylinositol-3 kinase also play a significant role. Signaling pathways for stimulation of transcription appeared quite diverse in that each gene was sensitive to different combination of inhibitors.
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