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1 Department of Anatomy and MRC for Cell Death Disease Research Center, Catholic University Medical College of Korea, Seoul, Korea, Republic of
2 Division of Nephrology, University of Maryland, Baltimore, MD, USA
* To whom correspondence should be addressed. E-mail: mkwon{at}medicine.umaryland.edu.
TonEBP is a transcriptional activator of the Rel family. In the renal medulla, TonEBP stimulates genes encoding proteins involved in cellular accumulation of organic osmolytes, the vasopressin regulated urea transporters (UT-A), and HSP70. To understand the role of TonEBP in the development of urinary concentrating ability, TonEBP expression during the rat kidney development was investigated. In embryonic kidneys, TonEBP immunoreactivity was detected 16 days post coitus in the cytoplasm of the endothelial cells surrounding the medullary collecting ducts (MCD). By 20 days, TonEBP was detected in most tubular profiles in the medulla including the loop of Henle and MCD, and interstitial cells. The intensity of TonEBP immunoreactivity was much higher in the vasa recta than the tubules. In addition, the immunoreactivity was localized predominantly to the cytoplasm. On postnatal day 1, two major changes were observed. TonEBP immunoreactivity shifted to the nucleus and the intensity of TonEBP immunoreactivity of the tubules increased dramatically. These changes were associated with an increase in TonEBP and SMIT mRNA abundance. Thereafter, TonEBP expression in tubular profiles increased moderately. Adult pattern of TonEBP expression was established at postnatal day 21 coincident with full maturation of the renal medulla. Thus, expression of TonEBP in developing kidneys occurred predominantly in the medulla and preceded expression of its target genes including UT-A. These data suggest that TonEBP contributes to the development of the urine concentrating ability.
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