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Articles in PresS, published online ahead of print March 26, 2002
Am J Physiol Renal Physiol, 10.1152/ajprenal.00332.2001
Submitted on October 31, 2001
Accepted on March 19, 2002
1 Department of Anatomy, The Catholic University of Korea, Seoul, Seoul, Korea, Republic of
2 Department of Anatomy, The Catholic University of Korea, Seoul, Seoul, Korea, Republic of; Department of Medicine, University of Florida College of Medicine, Gainesville, Florida, USA
3 Department of Veterinary Medicine, Chungnam National University, Daejeon, Daejeon, Korea, Republic of
4 Department of Medicine, University of Florida College of Medicine, Gainesville, Florida, USA
* To whom correspondence should be addressed. E-mail: jinkim{at}cmc.cuk.ac.kr.
Newborn rats are not capable of producing concentrated urine. With development of the concentrating system and a hypertonic medullary interstitium, intracellular osmolytes such as sorbitol accumulate in the renal medulla. Sorbitol is produced from glucose in a reaction catalyzed by aldose reductase (AR). The purpose of this study was to establish the time of expression and distribution of AR in the developing rat kidney. Kidneys from 16-, 18-, and 20-day-old fetuses and 1-, 3-, 4-, 5-, 7-, 14-, and 21-day-old pups were processed for immunohistochemistry and immunoblot analysis. In adult animals, AR was expressed only in the inner medulla, where it was localized in the ascending thin limb (ATL), inner medullary collecting duct (IMCD), and interstitial cells. AR immunoreactivity was not detected in fetal kidneys but was observed in the terminal part of the descending thin limb and IMCD in the renal papilla of one-day old pups. At birth, all of the loops of Henle are configured as short loops and there are no ATL. After birth, papillary thick ascending limbs (TAL) are gradually transformed into ATL by a process that involves apoptotic deletion of cells from the TAL. During this time, AR immunoreactivity appeared in the cells undergoing transformation in the ascending limb, beginning at the papillary tip and ascending to the border between outer and inner medulla. However, there was no labeling of apoptotic cells. The expression of AR in both ATL and IMCD gradually increased during kidney development. We conclude that AR expression in the inner medulla coincides with the increase in medullary tonicity that is known to occur during the first three weeks after birth. Based on the observation that only AR-negative cells were deleted by apoptosis in the differentiating ATL, we propose that AR may protect ATL cells against apoptosis.
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