The Perinatal Expression of Aquaporin-2 and Aquaporin-3 in Developing Kidney

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Title: The Perinatal Expression of Aquaporin-2 and Aquaporin-3 in Developing Kidney
Authors: Baum, Michelle A.; Ruddy, Marcella K.; Hosselet, Christine A.; Harris, H. William
Publisher: Pediatric Research
Date Published: June 01, 1998
Reference Number: 347
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The kidney provides an important contribution to permit the fetus to successfully transition to an independent existence by production of urine with significantly different osmolality compared with plasma. Although recent work has uncovered many aspects of the maturation and regulation of the renal concentrating and diluting mechanism, understanding of how alterations in the expression of aquaporin (AQP) water channels contribute to the formation of urine in the perinatal period is incomplete. Here, we report that both AQP-2 and -3 are expressed during fetal life as early as embryonic d 18 in ureteric buds of rat kidneys, where each is localized to the apical and basolateral membranes of epithelial cells, respectively. Northern analyses demonstrate that the 1.9-kb AQP-2 transcript is present in fetal and postnatal rat kidneys similar to that observed in adults. AQP-2 mRNA expression increases after d 3 of postnatal life. Immunoblotting reveals an increase in total kidney AQP-2 protein particularly with respect to its glycosylated form after postnatal d 3. AQP-3 protein also exhibits a similar alteration likely due to a similar increase in its glycosylation state. Both AQP-2 and AQP-3 display a distribution in the collecting ducts of human postnatal infants and adults identical to that exhibited in rat kidneys. These data show that both AQP-2 and -3 are present in collecting duct epithelia of fetal and postnatal kidneys. Thus, the reduced AVP-responsiveness and decreased urinary concentrating ability of the kidney during the fetal and immediate postnatal period does not appear to be caused by lack of AQP-2 or AQP-3 proteins.
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This translation by the NDI Foundation is to assist the lay reader. To provide a clear, accessible interpretation of the original article, we eliminated or simplified some technical detail and complicated scientific language. We concentrated our translation on those aspects of the article dealing directly with NDI. The NDI Foundation thanks the researchers for their work toward understanding and more effectively treating this disorder.
© Copyright NDI Foundation 2007 (JC)

As the fetus matures in utero, its kidneys gradually develop the ability to produce concentrated urine. However, the necessary maturation of this ability does not occur before, or immediately after, birth. Fetal and newborn animals generally produce unconcentrated urine for a while: 3 weeks in rats and rabbits and 2 - 12 months in humans. Researchers have suggested multiple factors that may contribute to the newborn's kidneys' inability to produce concentrated urine. In their study, Baum, et al., examine the appearance and development of aquaporin-2 (AQP2) and aquaporin-3 (AQP3) in both rat and human kidney.

Aquaporins (AQPs) are proteins that act as channels through which water can pass through cell membranes. There have been 10 different types of AQPs discovered in human tissue so far. Some are regulated by hormones: they wait for a hormonal signal before traveling to a specific cell membrane and inserting itself into it. Some are not regulated by hormones. AQP2 and AQP3 are both located in the kidney collecting duct (CD). AQP2 is regulated by the antidiuretic hormone, arginine vasopressin (AVP).

When AVP signals AQP2, AQP2 travels to the apical membrane of the principal cells in the kidney CD and inserts itself into it. This increases the water permeability (Pf) of the apical membrane and the kidney can then reabsorb the body water flowing through the CD. What liquid is not reabsorbed is concentrated urine that is later voided. AQP2 is located both in the cortical (outer) and medullary (inner) CDs. AQP3 is located in the basolateral membranes of the medullary CDs that express AQP2. Of course, the kidney doesn't appear fully formed, it too must develop gradually along with the rest of the fetus. During development, epithelial cells of the kidney undergo a complex series of processes that result in the formation of the nephrons, the main working units of the kidney.

Baum, et al., analyzing fetal, newborn and adult rat kidney tissue and adult and newborn human kidney tissue, found that AQP2 and AQP3 are expressed during fetal life as early as the 18th day in the rat embryo's life. As in later life, AQP2 is localized in the apical membrane and AQP3 in the basolateral membrane of the kidney CD cells. In rats, both AQP2 and AQP3 mRNA expression increases 3 days after birth, resulting in an increase in total kidney AQP2 and AQP3 protein (particularly AQP2s and AQP3s that have formed a linkage with glycosyl groups, i.e. that have undergone the process of glycosylation).

Rat AQP2 proteins alter somewhat during the initial 2 weeks of life. They progressively increase both the part of them that is glycosylated (a 4.5-fold increase) and the part that is not (1.5-fold increase). Thus, there are definite differences in glycosylation ratios between post natal and adult rat AQP2s, though the functional consequences of this difference, if any, is unknown. The tests on the rat AQP3 proteins suggest that they may also undergo alterations in their pattern of glycosylation similar to that displayed by rat AQP2.

Rat AQP2 protein increases more rapidly than AQP3. The authors believe this is due to the greater proportional growth and development of the kidney cortex (which is abundant in AQP2 but not AQP3) as compared to the kidney medulla (which is rich in both AQP3 and AQP2). The distribution of AQP2 and AQP3 in newborn and adult rats and newborn and adult humans is identical.

The authors' data indicates that the newborn rats' inability to form fully concentrated urine till sometime after birth is not due to a lack of AQP2 or AQP3 proteins.