1 Department of Anatomy, The Catholic University of Korea, Seoul 137-701; 3 Department of Veterinary Medicine, Chungnam National University, Daejeon, Korea; and 2 Department of Medicine, University of Florida College of Medicine, Gainesville, Florida 32610-02242
![]() |
ABSTRACT |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
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, in which it was localized in ascending thin limbs (ATLs), inner medullary collecting ducts (IMCDs), 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 1-day-old pups. At birth, all of the loops of Henle are configured as short loops and there are no ATLs. After birth, papillary thick ascending limbs are gradually transformed into ATLs by a process that involves apoptotic deletion of cells from the thick ascending limb. 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 the outer medulla and the inner medulla. However, there was no labeling of apoptotic cells. The expression of AR in both the ATL and the 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 3 wk after birth. On the basis of 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.
ascending thin limb; development; apoptosis
![]() |
INTRODUCTION |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
NEONATAL MAMMALS, INCLUDING rats, are unable to concentrate their urine, but develop this ability after birth (4). Urinary osmolality in neonatal rats rises from 300 mosmol/kgH2O at birth to nearly 2,000 mosmol/kgH2O by 3 wk of age (23, 32). With the development of the urine-concentrating system and the associated increase in osmolality in the renal papilla (9, 30), the cells in this region need to generate intracellular compatible osmolytes, such as sorbitol, myo-inositol, betaine, taurine, and glycerophosporylcholine, for the maintenance and regulation of the intracellular milieu (2, 12, 31). Sorbitol, one of these osmolytes, is produced from D-glucose in an NADPH-dependent reduction reaction catalyzed by aldose reductase (AR).
It is well known that AR activity correlates with intracellular sorbitol concentration and inner medullary osmolality (25, 26). In the adult rat kidney, AR activity is mainly found in the inner medulla and increases toward the papillary tip. There is no evidence of AR activity in the renal cortex and outer medulla. In the neonatal kidney, AR mRNA expression as well as enzyme activity in the inner medulla is significantly lower than in the adult kidney (1). Schwartz et al. (27) have demonstrated that AR mRNA and AR activity in terminal inner medullary collecting ducts (IMCDs) microdissected from developing rats increased dramatically during the first and second weeks after birth.
An increase in the ability to concentrate urine in the neonatal kidney is closely related to the morphological maturation of the renal papilla, especially the loop of Henle (9). In the neonatal kidney, the renal medulla is not separated into outer and inner zones. At the time of birth, ascending limbs with immature distal tubule epithelium are present throughout the renal medulla. All of the loops of Henle have the structural characteristics of the short loops of the adult kidney, and there are no ascending thin limbs (ATLs). Our laboratory (14) has previously demonstrated that immature thick ascending limbs (TALs) in the renal papilla are transformed into ATLs after apoptotic deletion of cells and differentiation of the remaining cells into a thin squamous epithelium. Thus the maturation of the loop of Henle and the development of a true inner medulla occur at the time of development of a hypertonic medullary interstitium.
In adult animals, it is well established that AR is expressed not only in the IMCD but also in the loop of Henle in the inner medulla (25, 29). However, little is known about the expression and distribution of AR in the developing kidney, and there is no information about AR in the differentiating loop of Henle. Therefore, our study was designed to establish the time of expression and the pattern of distribution of AR in the developing rat kidney, with special focus on the developing loop of Henle.
![]() |
METHODS |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Animals and Tissue Preservation
Sprague-Dawley rats were used in all experiments. The kidneys were obtained from 16-, 18-, and 20-day-old fetuses (E16, E18, and E20, respectively) and 1-, 3-, 4-, 5-, 7-, 14-, and 21-day-old pups (P1, P3, P4, P5, P7, P14, and P21, respectively). For each age group, three or four animals derived from two separate litters were used. The animals were anesthetized with an intraperitoneal injection of pentobarbital sodium (50 mg/kg). The kidneys were preserved by in vivo perfusion through the heart or abdominal aorta. The animals were initially perfused briefly with PBS (298 mosmol/kgH2O, pH 7.4) to rinse away blood. This was followed by perfusion with a periodate-lysine-2% paraformaldehyde 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 periodate-lysine-2% paraformaldehyde 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.Antibodies
AR immunoreactivity was detected using an affinity-purified goat polyclonal antibody against AR from rat lens (courtesy of Dr. Peter Kador, National Institutes of Health, Bethesda, MD). The antibody has been characterized in a previous study (29). The TAL was identified using a rabbit polyclonal antibody against the human serotonin receptor 5-hydroxytryptamine 1A (5-HT1A; courtesy of Dr. John Raymond, Duke University, Durham, NC). This antibody labels the basolateral plasma membrane of the TAL, distal convoluted tubule, and connecting tubule cells (24). The descending thin limb (DTL) of the loop of Henle was identified using a rabbit polyclonal antibody to aquaporin-1 (AQP1; courtesy of Dr. Mark A. Knepper, National Institutes of Health). This antibody labels the apical and basolateral plasma membrane of the proximal tubule and DTL (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 a total of 15 min. Before incubation with the primary antibody, the sections were pretreated with PBS containing 1% BSA, 0.05% saponin, and 0.2% gelatin (solution A) for 3 h. They were then incubated overnight at 4°C with antibodies to AR (1:100,000) or 5-HT1A (1:1,000) diluted in 1% BSA in PBS (solution B). The tissue labeled with antibodies against 5-HT1A is the same as that used in a previous study of the development of the ATL (14). Control incubations were performed in solution B lacking primary antibody. After three washes with solution A, the sections were incubated for 2 h in horseradish peroxidase-conjugated donkey anti-goat or anti-rabbit IgG Fab fragment (Jackson ImmunoResearch Laboratories, West Grove, PA) diluted 1:100 in solution B. The tissues were rinsed first in solution A and then 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 being washed with 0.05 M Tris buffer, the sections were dehydrated in a graded series of ethanol. From all animals, 50-µm-thick vibratome sections through the entire kidney were embedded in Poly/Bed 812 resin (Polysciences, Warrington, CA) sandwiched between polyethylene vinyl sheets.Double Labeling
From the flat-embedded vibratome sections of kidneys processed for immunohistochemical identification of TAL using 5-HT1A, different areas of the renal medulla were excised and glued onto an empty block of Poly/Bed 812 resin. Three consecutive 1.5-µm sections were cut for double immunolabeling for AR or AQP1 using a postembedding technique. The sections were 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. The sections were then rinsed with PBS, incubated in normal donkey serum (Jackson ImmunoResearch Laboratories) for 1 h, and subsequently incubated overnight at 4°C with antibodies to either AR or AQP1. After being washed in PBS, the sections were incubated for 2 h in peroxidase-conjugated donkey anti-goat or anti-rabbit IgG (Fab fragment) and washed again with PBS. For detection of AR and AQP1, Vector SG (Vector Laboratories, Burlingame, CA) was used as the chromogen to produce a gray-blue color, which is easily distinguished from the brown label produced by 3,3'-diaminobenzidine in the first immunolocalization procedure for 5-HT1A using the preembedding method (Table 1). The sections were washed with distilled water, dehydrated with graded ethanol and xylene, mounted in balsam, and examined by light microscopy.
|
Confocal Laser Scanning Microscopy
For immunofluorescence microscopy, kidney blocks containing all kidney zones were dehydrated and embedded in wax (polyethylene glycol 400 disterate, Polysciences). The wax-embedded tissues were cut to 5 µm on a rotary microtome (Leica), and the sections were dewaxed and rehydrated. In double-label fluorescent studies, AR was localized with goat polyclonal antibodies, which were mixed with rabbit antibodies against 5-HT1A or AQP1, respectively. The labeling was visualized using a fluorescein (FITC)-conjugated donkey-anti goat antibody (diluted 1:50; Jackson ImmunoResearch Laboratories) mixed with a Cy3-conjugated donkey anti-rabbit antibody (diluted 1:500; Jackson ImmunoResearch Laboratories). The microscopy was carried out using an MRC-1024 laser confocal microscope (Bio-Rad).Toluidine Blue Staining
Apoptotic cells were identified on 1.5-µm plastic sections of tissue processed for immunohistochemical identification of the TAL and DTL of Henle's loop. The sections were stained with toluidine blue, a vital dye known to stain cells undergoing apoptosis, and subsequently etched by incubation in a saturated solution of sodium hydroxide for 5 min, as described previously (14). After three brief rinses in absolute ethanol and a rinse with xylene, the sections were mounted in balsam and examined by light microscopy.Western Blot Analysis
The renal cortex and medulla from three animals in each age group were homogenized in lysis buffer containing 20 mM Tris · HCl, 1% Triton X-100, 150 mM sodium chloride, 0.5% sodium deoxycholate, 0.1% sodium dodecyl sulfate, 0.02% sodium azide, 1 mM EDTA, 10 µM leupeptin, and 1 mM phenylmethylsulfonyl fluoride. The homogenate was centrifuged at 3,000 g for 20 min at 4°C. After determination of protein concentration in the supernatant by the Coomassie method (Pierce, Rockford, IL), samples were loaded (30 µg/lane) and underwent electrophoresis on sodium dodecyl sulfate-polyacrylamide gels under reducing conditions. Proteins were transferred by electroelution to nitrocellulose membranes that had been blocked with 5% nonfat dry milk in PBS-T (0.1% Tween 20 in 0.01 M PBS, pH 7.4) for 30 min at room temperature, and the membranes were then incubated for 24 h at 4°C with affinity-purified anti-AR antibodies (1:100,000). The membranes were washed in several changes of PBS-T and incubated for 1 h with horseradish peroxidase-conjugated donkey anti-goat IgG (1:1,000). After a final washing, antibody labeling was visualized using an enhanced chemiluminescence system (Amersham Life Sciences, Buckinghamshire, UK) at room temperature. ![]() |
RESULTS |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Expression of AR in Adult Rat Kidney
AR immunoreactivity was present in the inner medulla, and there was no labeling in the cortex or outer medulla (Fig. 1A). Strong AR immunoreactivity was observed in the ATL, and there was an abrupt transition from the intensely labeled ATL to the AR-negative TAL, marking the border between the outer medulla and the inner medulla (Fig. 1, B and C). In the ATL, the intensity of AR immunoreactivity gradually decreased toward the tip of the papilla. AR was also expressed in the lower half of the IMCD and in interstitial cells in the deep papilla (Fig. 1D).
|
Expression of AR in Developing Rat Kidneys
Fetal kidney.
At E16, E18, and E20, no AR
immunoreactivity was detected in the cortex, outer medulla, or inner
medulla (Figs. 2A and
3A).
|
|
Neonatal rat kidney. AR-positive tubular profiles appeared first in the terminal part of the renal papilla at P1 and ascended gradually to the future border between the outer medulla and the inner medulla by 3 wk after birth (Figs. 2, B-F, and 3B).
By P1, all the loops of Henle had the configuration of short loops, and there were no ATLs (Fig. 2C). In the papillary tip, AR immunoreactivity was intense in the terminal part of the DTL (Fig. 3E), which was directly connected with the TAL, and weaker labeling was observed in the terminal part of the medullary collecting duct (Fig. 3B). To establish the exact sites of immunostaining for AR in the developing loop of Henle, a double-immunolabeling procedure was used in which the TAL and DTL were identified with antibodies to 5-HT1A and AQP1, respectively. In the base of the renal papilla, there was no AR immunoreactivity in the AQP1-positive DTL (Fig. 4, A and B). In contrast, there was little or no AQP1 immunoreactivity in the terminal part of the DTL in the papillary tip, in which AR immunolabeling was intense (Fig. 4, C and D). There was no AR immunoreactivity in 5-HT1A-positive TAL in the renal papilla at this age (Fig. 4, A-D).
|
|
|
Relationship of Expression of AR and Apoptosis in the Transforming Ascending Limb of the Loop of Henle
For identification of apoptosis by light microscopy, plastic sections were stained with toluidine blue followed by etching with a sodium hydroxide solution. To establish the exact sites of apoptosis in the transforming ascending limb of the loop of Henle, the TAL was identified by immunolabeling with an antibody to 5-HT1A using a preembedding method. This was followed by labeling on two consecutive 1.5-µm sections of the same tissue using a postembedding method. The first section was stained with toluidine blue for detection of apoptotic cells and apoptotic bodies, and the second section was used for detection of AR immunoreactivity.There were numerous apoptotic cells and apoptotic bodies in the
5-HT1A-positive TAL undergoing transformation in the renal papilla 2 wk after birth (Fig. 7). AR was
not expressed in apoptotic cells or apoptotic bodies, but there
was weak AR immunostaining in the remaining cells, which were
differentiating into the strongly AR-positive ATL epithelium (Fig. 7).
|
Western Blot Analysis
Determination of AR expression by immunoblotting revealed a band at 36.5 kDa (Fig. 8). AR protein was expressed in the renal medulla of both neonatal and adult rats. However, AR was not detected in either cortex or outer medulla from animals at any age examined. AR was not expressed in fetal kidneys, but a faint band was observed in protein from the renal medulla at postnatal day 1. Determination of the relative abundance of AR protein by densitometry demonstrated a gradual increase in AR expression during the first 3 wk after birth.
|
![]() |
DISCUSSION |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
The purpose of the present study was to determine the exact sites
of AR expression in the developing kidney, especially in the
differentiating loop of Henle, using specific markers to identify the
cells of the DTL and TAL. At all ages of animals examined, AR was
expressed only in the inner medulla, in which it was detected in both
ATL and IMCD. AR immunoreactivity was first observed in the terminal
part of the renal papilla in 1-day-old pups, and the intensity of
labeling gradually increased during the first 3 wk after birth. From 1 to 14 days of age, AR immunolabeling appeared in the transforming
ascending limb, beginning at the papillary tip and ascending to the
border between the outer medulla and the inner medulla (Fig.
9). In the transforming ascending limb
epithelium, AR was not observed in those cells undergoing apoptosis but was expressed weakly in the remaining cells,
which were differentiating into the strongly AR-positive ATL
epithelium. These findings suggest that AR may play a role in the
differentiation of the ATL. Moreover, it is noteworthy that the
expression of AR in the ATL and IMCD occurs during the first 2-3
wk after birth, when medullary tonicity is known to increase (23,
30).
|
The ability of the rat neonate to concentrate urine to adult levels is not reached until 3 wk after birth. There are a number of anatomical factors that contribute to the impaired concentrating ability of the neonatal kidney. Compared with adult, the neonate has poorly developed medullary vasa recta, abundant interstitial material in the medulla, and a shorter papilla in which there is no true inner medulla (30). The maturation of the concentrating system in the rat during the first 3 wk of postnatal life is associated with a lengthening of the renal papilla, including the long loops of Henle and the IMCD, and an increase in papillary sodium and urea concentrations (23, 32). Intracellular osmolytes, including sorbitol, are important for the maintenance of cellular functions in the hypertonic medullary interstitium, and sorbitol, which is generated from glucose by a process catalyzed by AR, is a major osmolyte in the inner medulla. In the neonatal rat, however, AR mRNA and activity in the inner medulla are significantly lower than in adult animals (1, 27).
It is well established that AR and various osmolyte transporters are induced by hyperosmotic stress (3, 12, 17, 31). Cells in the renal medulla are constantly exposed to steep osmotic gradients because of the high tonicity in the medullary interstitium required for the function of the urine-concentrating mechanism. Studies in cell lines derived from the inner medulla have demonstrated that increases in the osmolality of the medium are associated with increases in cellular sorbitol content, AR activity, and AR gene expression (6, 17, 21, 28). The mechanism for osmotic induction of AR gene transcription is not completely understood. Recently, however, Ferraris et al. (10), Ko et al. (16), and Daoudal et al. (7) identified a regulatory sequence element, the tonicity-responsive enhancer, in the AR gene of several species. Subsequently, Miyakawa et al. (20) characterized a tonicity-responsive enhancer binding protein, a transcription factor that regulates the expression of proteins catalyzing cellular accumulation of compatible osmolytes.
The role of osmotic stress in the induction of AR in the developing kidney is not known with certainty. Schwartz et al. (27) measured the changes in AR mRNA and activity in terminal IMCD microdissected from developing rat kidneys. These investigators found that AR mRNA and activity increased before a detectable increase occurred in urinary and inner medullary osmolality. On the basis of these observations, the authors concluded that the maturational induction of the AR gene was not a consequence of osmotic stimulation, but rather was part of the genetic program for the development of the kidney. However, it cannot be ruled out that small increases in inner medullary tonicity might have occurred that could not be detected. In this regard, it is noteworthy that a urea transporter is already expressed in the terminal IMCD 1 day after birth, suggesting that urea can be absorbed into the medullary interstitium in the distal part of the papilla shortly after birth (15).
Previous studies in adult animals have demonstrated AR immunoreactivity in Henle's loop and the collecting duct of the inner medulla, whereas no immunoreactivity was observed in the cortex (18, 29). These results are in general agreement with the results of our study. However, the distribution pattern of AR immunoreactivity in the ATL is different from that in the IMCD. In the adult rat kidney, the intensity of AR immunoreactivity in the ATL is very strong in the initial part of the inner medulla but gradually decreases toward the tip of the renal papilla. In contrast, there is strong AR immunoreactivity in the IMCD cells and interstitial cells in the terminal part of the inner medulla but little or no labeling in the initial part of the inner medulla. These results suggest that the expression of AR in the inner medulla may be dependent on other factors in addition to hyperosmolality, at least in the ATL, or may be differently regulated in different cell types in the renal medulla.
In neonatal rat kidneys, immunostaining for AR was also observed in the transforming ascending limb, beginning at the papilla tip and ascending to the border between the outer medulla and the inner medulla. At birth, all of the loops of Henle in the rat renal papilla are configured as short loops and there is no ATL. During the first 2-3 wk after birth, the ATL is developed from the 5-HT1A-positive epithelium of the primitive TAL by a process that involves apoptotic deletion of AR-negative cells from the TAL and differentiation of the remaining tubule cells into the flat 5-HT1A-negative, but AR-positive, epithelium of the ATL (14). On the basis of the observation that only AR-negative cells in the papillary ascending limb are deleted by apoptosis, it is tempting to speculate that AR expression in the remaining ascending limb cells may play a role in protecting these cells from undergoing apoptosis.
It is not known what initiates apoptosis in the TAL at the tip of the renal papilla shortly after birth and causes the process to proceed in an ascending manner through the renal medulla during the first 3 wk of age. The demonstration that apoptosis occurs in distinct regions of the renal medulla at different points in time suggests that the process is activated by localized changes in environmental factors that may occur around the time of birth. There is increasing evidence that hypertonic stress induces apoptosis. Michea et al. (19) and Dmitrieva et al. (8) demonstrated that cell-cycle delay and apoptosis were induced by high NaCl and/or urea in murine IMCD cells. Thus it is possible that the increase in medullary tonicity that occurs after birth plays a role in the activation of the apoptotic process.
The results of this study support the idea that AR plays an important role in the ability of renal medullary cells to adapt to osmotic stress during renal development in neonatal rats. It remains to be established whether high intracellular ionic strength has direct effects on AR gene transcription in the renal medulla during kidney development. Our studies of the relationship between AR expression and apoptosis in the ascending limb of Henle's loop suggest that AR may play a role in the differentiation of the ATL in the neonatal kidney. However, a direct relationship between AR and cell survival in the ascending limb remains to be established.
![]() |
ACKNOWLEDGEMENTS |
---|
We are grateful for the technical assistance of Hee-Duk Roh, Byung-Ouk Hong, and Kyung-A Ryu.
![]() |
FOOTNOTES |
---|
We acknowledge the financial support of the Korea Research Foundation (J. Kim) made in Program Year 1998. Part of this work has been published in abstract form (J Am Soc Nephrol 11: A0242, 2000).
Address for reprint requests and other correspondence: J. Kim, Dept. of Anatomy, Catholic Univ. of Korea, 505 Banpo-Dong, Seocho-Ku, Seoul 137-701, Korea (E-mail: jinkim{at}catholic.ac.kr).
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. Section 1734 solely to indicate this fact.
March 26, 2002;10.1152/ajprenal.00332.2001
Received 31 October 2001; accepted in final form 19 March 2002.
![]() |
REFERENCES |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
1.
Bondy, CA,
Lightman SL,
and
Lightman SL.
Developmental and physiological regulation of aldose reductase mRNA expression in renal medulla.
Mol Endocrinol
3:
1409-1416,
1989[Abstract].
2.
Burg, MB.
Role of aldose reductase and sorbitol in maintaining the medullary intracellular milieu.
Kidney Int
33:
635-641,
1988[ISI][Medline].
3.
Burger-Kentischer, A,
Muller E,
Neuhofer W,
Marz J,
Thurau K,
and
Beck F.
Expression of aldose reductase, sorbitol dehydrogenase and Na+/myo-inositol and Na+/Cl/betaine transporter mRNAs in individual cells of the kidney during changes in the diuretic state.
Pflügers Arch
437:
248-254,
1999[ISI][Medline].
4.
Calcagno, PL,
Rubib MI,
and
Weintraub DH.
Studies on the renal concentration and diluting mechanism in the premature infant.
J Clin Invest
33:
91-96,
1954[ISI].
5.
Corder, CN,
Colling JG,
Brannan TS,
and
Sharma J.
Aldose reductase and sorbitol dehydrogenase distribution in rat kidney.
J Histochem Cytochem
25:
1-8,
1977[Abstract].
6.
Cowley, BD,
Ferraris JD,
Carper D,
and
Burg MB.
In vivo osmoregulation aldose reductase mRNA, protein and sorbitol in renal medulla.
Am J Physiol Renal Fluid Electrolyte Physiol
258:
F154-F161,
1990
7.
Daoudal, S,
Tournaire C,
Halere A,
Veyssiere G,
and
Jean C.
Isolation of the mouse aldose reductase promoter and identification of a tonicity-responsive element.
J Biol Chem
272:
2615-2619,
1997
8.
Dmitrieva, N,
Kültz D,
Michea L,
Ferraris J,
and
Burg M.
Protection of renal inner medullary epithelial cells from apoptosis by hypertonic stress-induced p53 activation.
J Biol Chem
275:
18243-18247,
2000
9.
Edwards, BR,
Mendel DB,
LaRochelle FT,
Stern P,
and
Valtin H.
Postnatal development of urinary concentration ability in rat.
In: The Kidney During Development, edited by Spitzer A.. New York: Masson, 1982, p. 233-239.
10.
Ferraris, JD,
Williams CK,
Jung KY,
Bedfold JJ,
Burg MB,
and
Carcia-Perez A.
ORE, a eukaryotic minimal essential osmotic response element. The aldose reductase gene in hyperosmotic stress.
J Biol Chem
271:
18318-18321,
1996
11.
Gabbay, KH,
and
Cathcart ES.
Purification and immunological identification of aldose reductases.
Diabetes
23:
460-468,
1974[ISI][Medline].
12.
Garcia-Perez, A,
and
Burg MB.
Importance of organic osmolytes for osmoregulation by renal medullary cells.
Hypertension
16:
595-602,
1990[Abstract].
13.
Kern, TS,
and
Engerman RL.
Immunohistochemical distribution of aldose reductase.
Histochem J
14:
507-515,
1982[ISI][Medline].
14.
Kim, J,
Lee GS,
Tisher CC,
and
Madsen KM.
Role of apoptosis in development of the ascending thin limb of the loop of Henle in rat kidney.
Am J Physiol Renal Fluid Electrolyte Physiol
271:
F831-F845,
1996
15.
Kim, YH,
Kim DU,
Han KH,
Jung JY,
Sands JM,
Knepper MA,
Madsen KM,
and
Kim J.
Expression of urea transporters in the developing rat kidney.
Am J Physiol Renal Physiol
282:
F530-F540,
2002
16.
Ko, BC,
Ruepp B,
Bohren KM,
Gabbay KH,
and
Chung SS.
Identification and characterization of multiple osmotic response sequences in the human aldose reductase gene.
J Biol Chem
272:
16431-16437,
1997
17.
Kwon, HM,
and
Handler JS.
Cell volume regulated transporters of compatible osmolytes.
Curr Opin Cell Biol
7:
465-471,
1995[ISI][Medline].
18.
Ludvigson, MA,
and
Sorenson RL.
Immunohistochemical localization of aldose reductase. II. Rat eye and kidney.
Diabetes
29:
450-459,
1980[Abstract].
19.
Michea, L,
Ferguson DR,
Peters EM,
Andrews PM,
Kirby MR,
and
Burg MB.
Cell cycle delay and apoptosis are induced by high salt and urea in renal medullary cells.
Am J Physiol Renal Physiol
278:
F209-F218,
2000
20.
Miyakawa, H,
Woo SK,
Chen CP,
Dahl SC,
Handler JS,
and
Kwon HM.
Cis-and trans-acting factors regulating transcription of the BGT1 gene in response to hypertonicity.
Am J Physiol Renal Physiol
274:
F753-F761,
1998
21.
Moeckel, GW,
Lai LW,
Guder WG,
Kwon HM,
and
Lien YH.
Kinetics and osmoregulation of Na+- and Cl-dependent betaine transporter in rat renal medulla.
Am J Physiol Renal Physiol
272:
F100-F106,
1997
22.
Nielsen, S,
Smith BL,
Christensen EI,
Knepper MA,
and
Agre P.
CHIP 28 water channels are localized in constitutively water-permeable segments of the nephron.
J Cell Biol
120:
371-383,
1993[Abstract].
23.
Rane, S,
Aperia A,
Eneroth P,
and
Lundin S.
Development of urinary concentrating capacity in weaning rats.
Pediatr Res
19:
472-475,
1985[Abstract].
24.
Raymond, JR,
Kim J,
Beach RE,
and
Tisher CC.
Immunohistochemical mapping of cellular and subcellular distribution of 5-HT1A receptors in rat and human kidney.
Am J Physiol Renal Fluid Electrolyte Physiol
264:
F9-F19,
1993
25.
Sands, JM,
and
Schrader DC.
Coordinated response of renal medullary enzymes regulating net sorbitol production in diuresis and antidiuresis.
J Am Soc Nephrol
1:
58-65,
1990[ISI][Medline].
26.
Sands, JM,
Terada Y,
Bernard LM,
and
Knepper MA.
Aldose reductase activities in microdissected rat renal tubule segments.
Am J Physiol Renal Fluid Electrolyte Physiol
256:
F563-F569,
1989
27.
Schwartz, GJ,
Zavilowitz BJ,
Radice AD,
Garcia-Perez A,
and
Sands JM.
Maturation of aldose reductase expression in the neonatal rat inner medulla.
J Clin Invest
90:
1275-1283,
1992[ISI][Medline].
28.
Sone, M,
Ohno A,
Albrecht GJ,
Thurau K,
and
Beck FX.
Restoration of urine concentration ability and accumulation of medullary osmolytes after chronic diuresis.
Am J Physiol Renal Fluid Electrolyte Physiol
269:
F480-F490,
1995
29.
Terubayashi, H,
Sato S,
Nishimura C,
Kador PF,
and
Kinoshita JH.
Localization of aldose and aldehyde reductase in the kidney.
Kidney Int
36:
843-851,
1989[ISI][Medline].
30.
Trimble, ME.
Renal response to solute loading in infant rats: relation to anatomical development.
Am J Physiol
219:
1089-1097,
1970
31.
Yancey, PH,
and
Burg MB.
Distribution of major organic osmolytes in rabbit kidneys in diuresis and antidiuresis.
Am J Physiol Renal Fluid Electrolyte Physiol
257:
F602-F607,
1989
32.
Yasui, M,
Marples D,
Belusa R,
Eklof AC,
Celsi G,
Nielsen S,
and
Aperia A.
Development of urinary concentrating capacity: role of aquaporin-2.
Am J Physiol Renal Fluid Electrolyte Physiol
271:
F461-F468,
1996