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Am J Physiol Renal Physiol 276: F498-F509, 1999;
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Vol. 276, Issue 4, F498-F509, April 1999

Developmental expression of aquaporin 1 in the rat renal vasculature

Jin Kim1, Wan-Young Kim1, Ki-Hwan Han1, Mark A. Knepper2, Søren Nielsen3, and Kirsten M. Madsen4

1 Department of Anatomy, Catholic University Medical College, Seoul, Korea; 2 Laboratory of Kidney and Electrolyte Metabolism, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-0951; 3 Department of Cell Biology, Institute of Anatomy, University of Aarhus, DK-8000 Aarhus, Denmark; and 4 Division of Nephrology, Hypertension and Transplantation, University of Florida College of Medicine, Gainesville, Florida 32610-0224


    ABSTRACT
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

Aquaporin 1 (AQP-1) is a water channel protein that is constitutively expressed in renal proximal tubule and descending thin limb cells as well as in endothelial cells of the descending vasa recta. Studies in the developing rat kidney have demonstrated that AQP-1 is expressed in renal tubules before birth. However, nothing is known about the expression of AQP-1 in the renal vasculature during kidney development. The purpose of this study was to establish the distribution of AQP-1 in the renal vasculature of the developing rat kidney and follow the differentiation of the vascular system during kidney development. Kidneys from 16-, 17-, 18-, and 20-day-old fetuses and 1-, 4-, 7-, 14-, 21-, and 28-day-old pups were preserved and processed for immunohistochemical studies using a preembedding immunoperoxidase procedure. AQP-1 immunoreactivity was detected using affinity-purified rabbit polyclonal antibodies to AQP-1. AQP-1 was expressed throughout the arterial portion of the renal vasculature of the fetal and neonatal kidney from gestational age 17 days to 1 wk after birth. AQP-1 immunoreactivity gradually disappeared from the renal vasculature between 1 and 2 wk of age and remained only in the descending vasa recta. In contrast, AQP-1 immunoreactivity was not observed in lymphatic vessels until 3 wk of age and persisted in the adult kidney. AQP-1 was also expressed in a population of interstitial cells in the terminal part of the renal papilla at 3 wk of age as well as in the adult kidney. The transient expression of AQP-1 in the arterial portion of the renal vasculature in the developing rat kidney suggests that AQP-1 is important for fluid equilibrium and/or drainage in the developing kidney or, alternatively, plays a role in the regulation of growth and/or branching of the vascular tree during kidney development.

kidney development; vasa recta; renal lymphatics; immunohistochemistry


    INTRODUCTION
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

AQUAPORIN 1 (AQP-1) is a 28-kDa channel-forming integral membrane protein that belongs to the AQP family of membrane water channels (1, 8). AQP-1 was first discovered and purified from human erythrocytes by Agre and colleagues (5, 16, 19), and it is the major water channel in the erythrocyte membrane. AQP-1 is widely expressed in the plasma membrane of secretory and absorptive epithelia (1, 3, 13) as well as in nonfenestrated capillary endothelia (13) and is believed to play a major role in fluid transport throughout the body.

In the kidney, AQP-1 is heavily expressed in the apical and basolateral plasma membranes of the proximal tubule and the descending thin limb (14, 18), which are the constitutively water-permeable segments of the nephron. It has also been immunolocalized to the nonfenestrated endothelium of the descending vasa recta (12). In contrast, the ascending vasa recta, which have a fenestrated endothelium, do not express AQP-1 (12). In the human kidney, AQP-1 immunoreactivity has also been reported in the fenestrated endothelium of the glomerular capillaries and peritubular capillaries (10). However, in the vasculature of the normal adult rat kidney, AQP-1 has been observed only in the descending vasa recta.

Although the expression of AQP-1 and its segmental as well as cellular distribution in the kidney have been studied extensively, little is known about its expression and immunolocalization in the developing kidney, and there is no information about AQP-1 protein expression in the renal vasculature during development. In situ hybridization studies of AQP-1 expression in fetal and neonatal rats showed very little expression in the kidney before birth (2), and similar results were obtained in studies using ribonuclease protection assay (24). However, immunohistochemical studies demonstrated labeling for AQP-1 in both the proximal tubule and the descending thin limb of the fetal rat 3 days before birth (20). There is no information about AQP-1 immunoreactivity in the renal vasculature in the fetal kidney.

The presence of AQP-1 in the descending thin limb as well as in descending vasa recta is believed to play a major role in the urinary concentrating mechanism. Recent studies in transgenic mice lacking AQP-1 water channels have demonstrated a severe urinary concentrating defect, indicating that expression of AQP-1 is necessary for the development of a hypertonic medullary interstitium (9). Because rats are not able to concentrate their urine at birth, the original focus of this study was to determine whether AQP-1 was expressed in the renal medulla and particularly in the vasa recta of the fetal and neonatal kidney. The results of our initial studies revealed that, in contrast to observations in the adult kidney, in the developing kidney, AQP-1 is expressed in numerous blood vessels in the arterial part of the vascular system. Therefore, another purpose of this study was to establish the pattern of AQP-1 expression in the renal vasculature and follow the differentiation of the arterial vascular system in the developing rat kidney using AQP-1 as a marker.


    METHODS
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ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

Animals and tissue preservation. Sprague-Dawley rats were used in all experiments. Kidneys were obtained from 16 (E16)-, 17 (E17)-, 18 (E18)-, and 20-day-old (E20) fetuses and 1 (P1)-, 4 (P4)-, 7 (P7)-, 14 (P14)-, 21 (P21)-, and 28-day-old (P28) pups. The animals were anesthetized with a 50-mg/kg body wt intraperitoneal injection of pentobarbital sodium. The kidneys were preserved by in vivo perfusion through the heart or abdominal aorta. The animals were initially perfused briefly with PBS (osmolality 298 mosmol/kg H2O, pH 7.4) to rinse away all blood. This was followed by perfusion with a periodate-lysine-paraformaldehyde (PLP) solution for 5 min. After perfusion, the kidneys were removed and cut into 1- to 2-mm-thick slices that were fixed additionally by immersion in the PLP solution overnight at 4°C. Sections of tissue were cut transversely through the entire kidney on a vibratome at a thickness of 50 µm and processed for immunohistochemical studies using a horseradish peroxidase preembedding technique.

Antibody. Affinity-purified polyclonal antibody raised against a synthetic peptide corresponding to the terminal 22 amino acids of rat AQP-1 was used. This antibody recognizes AQP-1 in the rat kidney and has been characterized in detail previously (22).

Immunohistochemistry. Fifty-micrometer vibratome sections were processed for immunohistochemistry using an indirect preembedding immunoperoxidase method. All sections were washed with 50 mM NH4Cl in PBS three times for 15 min. Before incubation with the primary antibody, the sections were pretreated with a graded series of ethanol followed by incubation for 3 h with PBS containing 1% BSA, 0.05% saponin, and 0.2% gelatin (solution A). The tissue sections were then incubated overnight at 4°C with the antibody against AQP-1 diluted 1:300 in 1% BSA-PBS (solution B). Control incubations were performed in solution B without primary antibody. After several washes with solution A, the tissue sections were incubated for 2 h in peroxidase-conjugated goat anti-rabbit IgG Fab fragment (Jackson ImmunoResearch Laboratories) diluted 1:50 in solution B. The tissues were then rinsed, first in solution A and subsequently in 0.05 M Tris buffer, pH 7.6. For the detection of horseradish peroxidase, sections were incubated in 0.1% 3,3'-diaminobenzidine in 0.05 M Tris buffer for 5 min, after which H2O2 was added to a final concentration of 0.01% and the incubation was continued for 10 min. After washing with 0.05 M Tris buffer, the sections were dehydrated in a graded series of ethanol and embedded in Epon-812. From all animals, 50-µm-thick vibratome sections through the entire kidney were mounted in Epon-812 between polyethylene vinyl sheets. Sections of each part of the kidney from flat-embedded 50-µm-thick vibratome sections were excised and glued onto empty blocks of Epon-812. One-micrometer-thick sections were cut and treated for 5 min with a mixture of saturated sodium hydroxide and absolute ethanol (1:1) to remove the resin. After three brief rinses in absolute ethanol, the sections were hydrated with graded ethanol and rinsed in tap water. Some sections were counterstained with hematoxylin, whereas others were examined unstained. The sections were washed with distilled water, dehydrated with graded ethanol and xylene, mounted in balsam, and examined by light microscopy.


    RESULTS
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ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

Expression of AQP-1 in fetal kidneys. At E16, AQP-1 immunoreactivity was observed only in the renal cortex, where it was located in the endothelium of a few scattered capillary plexuses (Fig. 1). The AQP-1-positive capillary plexuses were located at the border between the nephrogenic zone and the renal medulla. In this area, AQP-1-negative capillary plexuses with wide lumina were frequently observed along the medullary side of the AQP-1-positive capillary plexuses. Small AQP-1-negative capillaries containing red blood cells were distributed throughout the cortex and medulla (Fig. 1).


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  		Fig. 1.   Light micrographs of a 50-µm-thick vibratome section (A) and a 1-µm-thick section (B) illustrating immunostaining for aquaporin 1 (AQP-1) in developing blood vessels in 16-day-old fetal kidneys. AQP-1 immunostaining is present in capillary plexus (arrows) in nephrogenic zone, at site of future arcuate arteries. Note absence of AQP-1 immunoreactivity in venous capillaries (arrowheads). MCD, medullary collecting duct. Magnifications: A, ×135; B, ×250.

At E17, the arcuate artery at the border between the nephrogenic zone and the medulla exhibited strong AQP-1 immunoreactivity (Fig. 2). AQP-1 was also expressed in the endothelium of small blood vessels extending from the arcuate artery into the renal cortex and medulla. From the blood vessels that ascended into the cortex, several AQP-1-positive branches extended to developing nephrons, including renal vesicles and S-shaped bodies. At the corticomedullary junction, AQP-1-positive small vessels extending from the arcuate artery formed the afferent arterioles of the juxtamedullary glomeruli. In addition, many AQP-1-positive vessels descended directly from the arcuate artery into the deep part of the medulla and formed capillary plexuses surrounding the medullary collecting ducts (Fig. 3). However, AQP-1 immunoreactivity was not observed in the venous system, including the arcuate vein (Fig. 4, A and B). In addition to being expressed in blood vessels, AQP-1 immunoreactivity appeared in the proximal anlage of juxtamedullary nephrons at this age (Figs. 2 and 3).


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  		Fig. 2.   Light micrographs of a 50-µm-thick vibratome section illustrating immunostaining for AQP-1 in 17-day-old fetal kidney. AQP-1 is expressed in arcuate artery (AA) and in small blood vessels extending from AA to developing nephrons (arrowheads) and into medulla (open arrow). Area marked by a rectangle in A is shown at higher magnification in B. Note immunoreactivity for AQP-1 in proximal tubule (PT; solid arrows) anlage. Magnifications: A, ×80; B, ×165.


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  		Fig. 3.   Light micrographs of 50-µm-thick vibratome section (A) and 1-µm-thick sections (B and C) illustrating immunostaining for AQP-1 in 17-day-old fetal kidneys (A-C). A and B: MCD is surrounded by AQP-1-positive capillary plexus (arrows), which is connected with small blood vessels (arrowheads) extending from AA. C: AQP-1 immunostaining in afferent arteriole (aa) of a juxtamedullary glomerulus. There is no immunoreactivity in arcuate vein (AV) or in developing glomerular capillaries. Magnifications: A, ×170; B and C, ×420.


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  		Fig. 4.   Light micrographs of 50-µm-thick vibratome sections (A and D) and 1-µm-thick sections (B and C) illustrating immunostaining for AQP-1 in renal cortex from 17-day-old fetus (A and B) and 14 (C)- and 21-day-old (D) pups. AQP-1 is expressed in apical and basolateral plasma membrane of endothelial cells in AA in fetal kidneys (A and B) but gradually disappears after birth (C and D). Note absence of AQP-1 immunoreactivity in AV at all ages. D: AQP-1-positive lymphatic vessels (arrows) are located in connective tissue sheath surrounding AA. Arrowheads indicate AQP-1-negative capillaries in developing glomeruli. Magnifications: A, ×300; B, ×460; C, ×370; D, ×460.

At E18 and E20, AQP-1 was expressed in the endothelium of arcuate arteries, interlobular arteries, and afferent arterioles in the renal cortex (Fig. 5A). In the medulla, AQP-1-positive descending vasa recta extended into the papillary tip and were loosely connected to each other by small branches (not shown). At these ages, the AQP-1 immunoreactivity in the blood vessels was decreased in intensity compared with the labeling at E16 and E17. There was no AQP-1 immunoreactivity in the efferent arterioles of cortical glomeruli. However, a transient expression of AQP-1 was observed in efferent arterioles of juxtamedullary glomeruli at E20 (Fig. 6A).


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  		Fig. 5.   Light micrographs of 50-µm-thick vibratome sections illustrating immunostaining for AQP-1 in kidneys from 20-day-old fetus (A) and 7 (B)-, 14 (C)-, and 21-day-old (D) pups. A: in fetal kidney, AQP-1 is expressed in entire arterial tree (arrowheads), including AA. AQP-1 is expressed in interlobular arteries (IA) and aa until 7 days of age (B) and then gradually disappears. Note AQP-1-negative IA and aa in 14 (C)- and 21-day-old (D) kidneys. Magnifications in A-D, ×460.


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  		Fig. 6.   Light micrographs of 50-µm-thick vibratome sections illustrating AQP-1 immunostaining in kidneys from 20-day-old fetus (A) and 4-day-old pup (B). A: AQP-1 is expressed in efferent arteriole (ea) of a juxtamedullary glomerulus as well as in aa and AA in the 20-day-old fetus. B: AQP-1-negative ea is connected with AQP-1-positive descending vasa recta (arrowheads). Magnifications in A and B, ×460.

Expression of AQP-1 in neonatal kidneys. In 1-, 4-, and 7-day-old pups, there was a gradual decrease in AQP-1 immunoreactivity in the arcuate artery but AQP-1 was still expressed in interlobular arteries and afferent arterioles (Figs. 5B and 7A). Weak AQP-1 immunostaining was also observed in efferent arterioles of juxtamedullary glomeruli from P1, but there was no labeling of efferent arterioles from P4 (Fig. 6B) or P7. In the renal medulla, there was an increase in the number of AQP-1-positive descending vasa recta after birth (Fig. 7, A and B). However, they did not form vascular bundles at this age (Fig. 7B). On 50-µm-thick vibratome sections from P4 and P7, it was apparent that most of the AQP-1-positive descending vasa recta were connected with the AQP-1-negative efferent arterioles of juxtamedullary glomeruli (Fig. 6B).


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  		Fig. 7.   Light micrographs of 50-µm-thick vibratome sections illustrating immunostaining for AQP-1 in kidneys from 1 (A)-, 7 (B)-, 14 (C)-, and 21-day-old (D) pups. A: AQP-1 immunoreactivity is present in entire arterial tree (solid arrow) and in descending vasa recta (open arrow) in 1-day-old pup. There was a gradual increase in AQP-1-positive vasa recta during development, but vascular bundles (VB) were not formed until 14 days after birth (C) and were fully developed at 21 days of age (D). Arrowheads indicate AQP-1-positive descending thin limbs of Henle's loop. Magnifications: A, ×120; B-D, ×180.

In 14- and 21-day-old pups, there was no immunoreactivity for AQP-1 in the arcuate or interlobular arteries or afferent arterioles (Figs. 4C and 5, C and D). In the renal vasculature, AQP-1 was expressed only in descending vasa recta, which gradually increased in number (Fig. 7, C and D). Vascular bundles were not observed until 14 days after birth and were fully developed at 21 days of age (Fig. 7D). In 21-day-old pups, AQP-1 immunoreactivity was also observed in a small number of interstitial cells in the terminal part of the renal papilla (Fig. 8B) as well as in lymphatic vessels in the renal cortex (Fig. 9A).


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  		Fig. 8.   Light micrographs of 50-µm-thick vibratome sections (A-C) and a 1-µm-thick section (D) illustrating immunostaining for AQP-1 in terminal part of renal papilla from 14 (A)- and 21-day-old (B) pups and adult rats (C and D). AQP-1-positive interstitial cells (arrowheads) were observed at terminal part of renal papilla from 21 days of age (B). Note AQP-1 immunoreactivity on plasma membrane of cell body and processes of some interstitial cells (D). Arrows indicate AQP-1-negative interstitial cells. Magnifications: A and B, ×180; C, ×230; D, ×920.


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  		Fig. 9.   Light micrographs of 50-µm-thick vibratome sections (A, B, and C) and a 1-µm-thick section (D) illustrating immunostaining AQP-1 in renal cortex from 21 (A)- and 28-day-old (B) pups and adult rat (C and D). A: AQP-1 is expressed in lymphatic vessels (open arrow) from 21 days of age. B: AQP-1 appeared in lymphatic vessels (arrows) along aa and IA from 28 days of age. Note AQP-1-positive lymphatic vessels (arrows) along IA in adult kidneys (C and D). Magnifications in A-D, ×460.

In the renal cortex of 28-day-old pups as well as that of adult rats, besides the strong labeling of proximal tubules, AQP-1 was expressed only in lymphatic vessels in the periarterial connective tissue sheath along the interlobular and arcuate arteries (Fig. 9). The intensity of labeling in the lymphatic vessels was very weak compared with that observed in the proximal tubule (Fig. 9, B-D). There was no immunoreactivity for AQP-1 in arcuate arteries, interlobular arteries, or afferent arterioles. In the medulla, AQP-1 immunostaining was observed in the descending vasa recta and in a subpopulation of interstitial cells in the terminal part of the renal papilla in addition to the labeling of thin descending limbs of Henle's loop (Fig. 8, C and D). The AQP-1-positive interstitial cells were few in number and possessed many slender cytoplasmic processes with globular terminal endings that appeared to be connected with neighboring tubules.

AQP-1 immunoreactivity was not observed in glomerular and peritubular capillaries or venous blood vessels in the developing kidney at any of the ages examined (Figs. 1B, 3C, and 4).


    DISCUSSION
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

The present study provides the first description of AQP-1 expression in the vascular system of the developing kidney. Although previous studies have demonstrated low levels of AQP-1 mRNA (2, 24) and protein (20) in both the proximal tubule and descending thin limb of the developing rat kidney before birth, those studies provided no information about AQP-1 expression in the renal vasculature.

The results of our study revealed that in the fetal kidney, AQP-1 is expressed not only in proximal tubules and descending thin limbs of Henle's loop but throughout the arterial portion of the renal vasculature, including arcuate arteries, interlobular arteries, and afferent arterioles, as well as in the descending vasa recta (see Fig. 10). This distribution is in contrast to observations in the adult rat kidney, in which AQP-1, in addition to its expression in renal tubules (14, 18), has been described only in the descending vasa recta (12). Studies by Nielsen and co-workers (12) demonstrated that in the adult rat kidney, AQP-1 is expressed in the nonfenestrated endothelium of the descending vasa recta, which is consistent with the high water permeability of these vessels. However, there is no evidence that AQP-1 is present in other parts of the vascular system of the adult rat kidney. Surprisingly, AQP-1 expression in the arcuate arteries, interlobular arteries, and afferent arterioles was gradually downregulated after birth and had disappeared at 2 wk of age (Fig. 10). In contrast, AQP-1 immunoreactivity in the descending vasa recta, which appeared at E18, persisted after birth and increased in intensity in a fashion similar to that observed in the proximal tubule and descending thin limb and reported previously by other investigators (20).


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  		Fig. 10.   Diagram illustrating changes in AQP-1 immunostaining along renal vasculature of developing rat kidney. AQP-1 immunoreactivity is indicated by black color in blood vessels and lymphatic vessels. AVR, ascending vasa recta CP, capillary plexus; DVR, descending vasa recta; G, glomerulus; LV, lymphatic vessel; d, day.

Previous studies have provided evidence that AQP-1 in the descending vasa recta is involved in transendothelial water transport (15). However, the exact functional significance of this observation is not known with certainty. The demonstration that AQP-1 remains in the descending vasa recta, whereas it disappears in the other parts of the renal vasculature after birth, suggests that it may be important for the function of the descending vasa recta. It is noteworthy that a striking increase in the level of AQP-1 expression in the descending vasa recta as well as in the proximal tubule and descending thin limb of Henle's loop occurs during the first 3 wk after birth and coincides with the development of the renal concentrating mechanism (7, 17, 23). Moreover, a recent study (9) in transgenic mice lacking AQP-1 demonstrated a severe impairment of the urinary concentrating ability, suggesting that AQP-1 is necessary for the development of a hypertonic medullary interstitium. Interestingly, a transient weak expression of AQP-1 was also observed in efferent arterioles of juxtamedullary glomeruli that give rise to the AQP-1-positive descending vasa recta. However, AQP-1 immunoreactivity was not observed in efferent arterioles after 4 days of age, although it remained in the descending vasa recta.

The functional significance of the transient expression of AQP-1 in the arterial part of the renal vascular system during kidney development is not known. However, it should be pointed out that the vascular system is not fully developed at the time when AQP-1 is expressed in the arterial system. Therefore, a possible function of AQP-1 in the developing kidney may be to prevent localized fluid build up by providing a means of drainage at a time when there appear to be no functional lymphatic vessels. Another putative function of AQP-1 would be to allow fluid to equilibrate across the wall of sprouting vessels that may in part consist of distally closed structures at this time. It is also possible that AQP-1 is involved in the regulation of growth and/or branching of the arterial vascular tree during kidney development. In a previous study by Bondy and co-workers (2), a transient expression of AQP-1 mRNA was observed in the periosteum surrounding developing bone, in developing endocardium, and in the fetal cornea. However, the physiological importance of the transient expression of AQP-1 in these tissues during development remains to be established. Finally, it should be mentioned that a protein does not necessarily play an important role at all sites where it is expressed. There are several reports of superfluous expression of proteins in cells or tissues where they have no apparent function (6).

Because AQP-1 was expressed throughout the arterial system of the developing rat kidney, immunostaining for AQP-1 using a preembedding method and plastic-embedded tissue made it possible to follow the differentiation of the renal vasculature during kidney development. The results indicate that the arterial vascular system in the kidney cortex is derived from primitive capillary networks that could be distinguished already at E16 at the sites of the future arcuate arteries and by E17 had differentiated into arcuate arteries, interlobular arteries, and sprouting afferent arterioles.

This study also revealed the presence of AQP-1-positive vessels descending directly from the arcuate artery, forming so-called true vasa recta vera. These vessels descended into the deep part of the medulla, where they continued into a capillary plexus surrounding the medullary collecting duct. Vasa recta vera have been described previously in the rat kidney but were observed only in old animals (4, 21). It was suggested in those studies that vasa recta vera may develop secondary to glomerular degeneration. In the present study, AQP-1-positive vasa recta vera were observed only in the fetal kidney. It is not known whether these vessels disappeared after birth or we failed to recognize them because of the downregulation of AQP-1. However, true vasa recta vera are not believed to exist in normal young adult rats.

From 21 days of age, AQP-1 was expressed in lymphatic vessels located in the periarterial connective tissue along arcuate and interlobular arteries. However, AQP-1-positive lymphatics were not observed in the fetal or neonatal kidney. Thus the initial expression of AQP-1 in lymphatic vessels in the renal cortex appears to coincide with or follow the downregulation and disappearance of AQP-1 from the arterial portion of the renal vasculature. The demonstration of AQP-1 in lymphatic vessels in the renal cortex confirms observations in the adult kidney reported previously (12). Expression of AQP-1 in lymphatic vessels has also been reported in other tissues, including the intestine (13).

The role of AQP-1 in interstitial cells in the terminal part of the renal papilla is not known. However, it is possible that AQP-1 is involved in osmotic regulation in these cells. Under the experimental conditions of the present study, AQP-1 appeared to be expressed in only a few of the interstitial cells in the renal papilla. Whether the differential expression of AQP-1 indicates the presence of different types of interstitial cells or simply reflects different functional states of the same cell type remains to be explored. The presence of AQP-1 in interstitial cells is consistent with the results of previous studies in which AQP-1 immunoreactivity was observed in fibroblasts along the respiratory tract and nasopharynx (11).

In summary, the results of this study demonstrate that AQP-1 is transiently expressed in the arterial portion of the renal vascular system during development and remains only in the descending vasa recta after 2 wk of age. In addition to the well-established expression in proximal tubules, thin descending limbs of Henle's loop, and descending vasa recta, AQP-1 is present in lymphatic vessels of the renal cortex and in a population of interstitial cells in the terminal renal papilla at 3 wk of age as well as in adult kidney. These observations suggest that AQP-1 plays an important role during the development and differentiation of the renal vasculature.


    ACKNOWLEDGEMENTS

We gratefully acknowledge the technical assistance of Byung-Ouk Hong, Hee-Duk Roh, Wendy Wilber, and Li Zhang.


    FOOTNOTES

This work was supported by Korean Ministry of Health and Welfare Grant HMP-96-M-2-1037 and National Institute of Diabetes and Digestive and Kidney Diseases Grant DK-28330.

Address for other correspondence: K. M. Madsen, Division of Nephrology, Hypertension and Transplantation, PO Box 100224, Univ. of Florida, Gainesville, FL 32610-0224 (E-mail: madsekm{at}medicine.ufl.edu).

The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.

Address for reprint requests: J. Kim, Dept. of Anatomy, Catholic Univ. Medical College, 505 Banpo-Dong, Socho-Ku, Seoul 137-701, Korea (E-mail: jinkim{at}cmc.cuk.ac.kr).

Received 26 August 1998; accepted in final form 17 November 1998.


    REFERENCES
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

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2.   Bondy, C., E. Chan, B. L. Smith, G. M. Preston, and P. Agre. Developmental gene expression and tissue distribution of the CHIP28 water-channel protein. Proc. Natl. Acad. Sci. USA 90: 4500-4504, 1993[Abstract/Free Full Text].

3.   Brown, D., J. M. Verbavatz, G. Valenti, B. Lui, and I. Sabolic. Localization of the CHIP28 water channel in reabsorptive segments of the rat reproductive tract. Eur. J. Cell Biol. 61: 264-273, 1993[Medline].

4.   Casellas, D., and A. Mimran. Shunting in renal microvasculature of the rat: a scanning electron microscopic study of corrosion casts. Anat. Rec. 201: 237-248, 1981[Medline].

5.   Denker, B. M., B. L. Smith, F. P. Kuhajda, and P. Agre. Identification, purification, and partial characterization of a novel Mr 28,000 integral membrane protein from erythrocytes and renal tubules. J. Biol. Chem. 263: 15634-15642, 1988[Abstract/Free Full Text].

6.   Erickson, H. P. Gene knockouts of c-src, transforming growth factor beta 1, and tenascin suggest superfluous, nonfunctional expression of proteins. J. Cell Biol. 120: 1079-1081, 1993[Free Full Text].

7.   Falk, G. Maturation of renal function in infant rats. Am. J. Physiol. 181: 157-170, 1955.

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Am J Physiol Renal Physiol 276(4):F498-F509
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