Developmental expression of aquaporin 1 in the rat renal vasculature

1999 ◽  
Vol 276 (4) ◽  
pp. F498-F509 ◽  
Author(s):  
Jin Kim ◽  
Wan-Young Kim ◽  
Ki-Hwan Han ◽  
Mark A. Knepper ◽  
Søren Nielsen ◽  
...  

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.

1997 ◽  
Vol 272 (5) ◽  
pp. F579-F586 ◽  
Author(s):  
T. L. Pallone ◽  
M. R. Turner

Molecular sieving of small solutes by outer medullary descending vasa recta (OMDVR). Descending vasa recta (DVR) plasma equilibrates with the medullary interstitium by volume efflux (Jv), as well as by influx of solutes. Jv is driven by transmural osmotic pressure gradients due to small hydrophilic solutes (delta pi s), NaCl and urea. DVR endothelium probably contains a "water-only" pathway most likely mediated by the aquaporin-1 (AQP1) water channel. We measured the ability of microperfused OMDVR to concentrate lumenal 22Na and [3H]raffinose when Jv was driven by transmural NaCl gradients. Collectate-to-perfusate ratios of 2 x 10(6) M(r) fluorescein isothiocyanate-labeled dextran volume marker (RDx), 22Na (RNa), and [3H]raffinose (Rraf) were measured in the absence and presence of Jv. During volume efflux (Jv > 0), RDx was 1.37 +/- 0.31. RNa increased from 0.64 +/- 0.03 when Jv = 0 to 0.82 +/- 0.05 when Jv > 0 and Rraf increased from 0.83 +/- 0.03 to 1.13 +/- 0.05: Mathematical simulations predict RNa and Rraf most accurately when the OMDVR reflection coefficient to the tracers is assigned a value near unity. This indicates that the OMDVR wall contains a pathway for osmotic volume flux that excludes small hydrophilic solutes, a behavior consistent with that of aquaporins.


1974 ◽  
Vol 22 (11) ◽  
pp. 1034-1038 ◽  
Author(s):  
CLINTON N. CORDER ◽  
MARK L. BERGER ◽  
OLIVER H. LOWRY

Quantitative histochemical measurements of two enzymes of uridine diphosphoglucose (UDPG) metabolism have been made in the developing rat kidney nephron. Kidneys were examined from -4 days to 44 days of age. In the adult kidney, UDPG-pyrophosphatase was concentrated in proximal convoluted and straight tubules. During maturation, activity decreased in glomeruli, increased in the proximal tubule and changed little elsewhere in the nephron. UDPG-pyrophosphorylase revealed a different pattern. Activity was more nearly uniformly distributed throughout the nephron but was highest in the proximal straight tubule and ascending limb of Henle. During development, activity was unchanged or increased in glomeruli and small arteries and increased elsewhere, particularly in the proximal straight tubule and ascending limb of Henle.


1992 ◽  
Vol 263 (6) ◽  
pp. C1225-C1233 ◽  
Author(s):  
I. Sabolic ◽  
G. Valenti ◽  
J. M. Verbavatz ◽  
A. N. Van Hoek ◽  
A. S. Verkman ◽  
...  

CHIP28 is an integral membrane protein that has been identified as the erythrocyte water channel and that is also expressed in the kidney. Antibodies against erythrocyte CHIP28 were used to localize this protein along the rat urinary tubule. By Western blotting, CHIP28 was detected in kidney plasma membrane and endosome fractions. With the use of immunocytochemistry, CHIP28 was located in brush-border and basolateral plasma membranes of the proximal tubule. The initial S1 segment was weakly stained, but the S2 and S3 segments were heavily labeled. Subapical vesicles were also positive. Apical and basolateral membranes of the long thin descending limb were strongly labeled, but ascending thin and thick limbs of Henle and distal convoluted tubules were negative. Some vasa recta profiles in the medulla were positive. CHIP28 is, therefore, present in membranes with a high constitutive water permeability, where it probably acts as a transmembrane water-conducting channel. Finally, a weak staining of apical and basolateral membranes of cortical collecting duct principal cells was detectable, suggesting a potential relationship of CHIP28 to the vasopressin-sensitive water channel.


1997 ◽  
Vol 272 (5) ◽  
pp. F587-F596 ◽  
Author(s):  
T. L. Pallone ◽  
B. K. Kishore ◽  
S. Nielsen ◽  
P. Agre ◽  
M. A. Knepper

Outer medullary descending vasa recta (OMDVR) were perfused in vitro, and volume efflux was measured by driving water movement with transmural gradients of NaCl or albumin. Consistent with mediation by water channels, p-chloromercuribenzenesulfonic acid (pCMBS) markedly inhibited volume flux induced by NaCl. Dithiothreitol reversed the inhibition, pCMBS did not significantly alter water flux induced by albumin. Osmotic water permeability (Pf) of the pCMBS-sensitive pathway of glutaraldehyde-fixed and nonfixed OMDVR was 1,102 +/- 449 and 1,257 +/- 718 microns/s (means +/- SD), respectively. pCMBS reduced Pf to near zero, whereas diffusional water permeability in the same vessels was only slightly inhibited. Immunoreactive aquaporin-1 (AQP1) measured by enzyme-linked immunosorbent assay in collagenase-treated and untreated OMDVR was 5.2 +/- 1.0 and 4.2 +/- 0.4 fmol/mm, respectively, values that account well for the experimental Pf. We conclude that OMDVR water flux driven by NaCl gradients is most likely mediated by the AQP1 water channel and that NaCl and urea gradients drive water efflux in vivo by this route.


Development ◽  
1993 ◽  
Vol 118 (3) ◽  
pp. 777-784 ◽  
Author(s):  
H.S. Coles ◽  
J.F. Burne ◽  
M.C. Raff

Although normal cell death is known to occur in many developing vertebrate organs, it has not been thought to play an important part in the development of the mammalian kidney. We show here that normal cell death is found in both the nephrogenic region and medullary papilla of the developing rat kidney and, in each of these areas, it follows a distinct developmental time course. As many as 3% of the cells in these areas have a typical apoptotic morphology and the dead cells seem to be cleared rapidly (within 1–2 hours) by phagocytosis by neighbouring parenchymal cells. These values are similar to those in vertebrate neural tissues where 50% or more of the cells die during normal development, suggesting that large-scale death is a normal feature of kidney development. We also show that in vivo treatment with epidermal growth factor inhibits cell death in the developing kidney, consistent with the possibility that the cells normally die because they lack sufficient survival factors. Our findings suggest that the extent of normal cell death in developing animals is still greatly underestimated and they raise the possibility that many of these cell deaths may reflect limiting amounts of survival factors.


1995 ◽  
Vol 268 (6) ◽  
pp. F1023-F1037 ◽  
Author(s):  
S. Nielsen ◽  
T. Pallone ◽  
B. L. Smith ◽  
E. I. Christensen ◽  
P. Agre ◽  
...  

The localization of aquaporin-1 water channels (AQP-1) in nephron and vascular structures in rat kidney were characterized, because vascular bundles are known to play a key role in urinary concentration. Immunohistochemistry and immunoelectron microscopy were applied on thin cryosections or ultrathin Lowicryl sections, using an optimized freeze-substitution method. Within the vascular bundles, AQP-1 is localized in descending thin limbs (DTL) of short nephrons in apical and basolateral membranes. The expression in DTL of short nephrons is considerably lower compared with the expression in long nephrons, consistent with the known lower osmotic water permeability of this segment. Furthermore, DTL of short nephrons expressing AQP-1 continue abruptly into a thin limb segment without AQP-1. This suggests the existence of a novel thin limb epithelium in the outer medulla. Extensive expression of AQP-1 is observed in apical and basolateral membranes of DTL of long nephrons, which are localized in the periphery of the vascular bundles. The expression decreases along the axis of long nephron DTLs in correlation with the known water permeability characteristics of thin limb segments. DTLs of both short and long nephrons continue abruptly into thin limb segments without AQP-1 expression, revealing an abrupt cell-to-cell transition. In vasa recta, AQP-1 is selectively localized in the nonfenestrated endothelium of descending vasa recta, whereas the fenestrated endothelium of ascending vesa recta and peritubular capillaries do not express AQP-1. AQP-1 is localized in both apical and basolateral plasma membranes, which is logical for transendothelial water transport. Isolated perfused descending vasa recta display high water permeability, and, unlike sodium permeability, diffusional water permeability is partly inhibited by mercurials, thus substantiating the presence of mercurial-sensitive water channels in descending vasa recta. Thus AQP-1 is localized in DTL and descending vasa recta within vascular bundles, and AQP-1 expression in DTL segments is in exact concordance with the known water permeability characteristics, strongly supporting that AQP-1 is the major constitutive water channel of the nephron.


2002 ◽  
Vol 282 (3) ◽  
pp. F530-F540 ◽  
Author(s):  
Young-Hee Kim ◽  
Dong-Un Kim ◽  
Ki-Hwan Han ◽  
Ju-Young Jung ◽  
Jeff M. Sands ◽  
...  

Urea transport in the kidney is mediated by a family of transporter proteins that includes renal urea transporters (UT-A) and erythrocyte urea transporters (UT-B). Because newborn rats are not capable of producing concentrated urine, we examined the time of expression and the distribution of UT-A and UT-B in the developing rat kidney by light and electron microscopic immunocytochemistry. Kidneys from 16-, 18-, and 20-day-old fetuses, 1-, 4-, 7-, 14-, and 21-day-old pups, and adult animals were studied. In the adult kidney, UT-A was expressed intensely in the inner medullary collecting duct (IMCD) and terminal portion of the short-loop descending thin limb (DTL) and weakly in long-loop DTL in the outer part of the inner medulla. UT-A immunoreactivity was not present in the fetal kidney but was observed in the IMCD and DTL in 1-day-old pups. The intensity of UT-A immunostaining in the IMCD gradually increased during postnatal development. In 4- and 7-day-old pups, UT-A immunoreactivity was present in the DTL at the border between the outer and inner medulla. In 14- and 21-day-old pups, strong UT-A immunostaining was observed in the terminal part of short-loop DTL in the outer medulla, and weak labeling remained in long-loop DTL descending into the outer part of the inner medulla. In the adult kidney, there was intense staining for UT-B in descending vasa recta (DVR) and weak labeling of glomeruli. In the developing kidney, UT-B was first observed in the DVR of a 20-day-old fetus. After birth there was a striking increase in the number of UT-B-positive DVR, in association with the formation of vascular bundles. The intensity of immunostaining remained strong in the outer medulla but gradually decreased in the inner medulla. We conclude that the expression of urea transporters in short-loop DTL and DVR coincides with the development of the ability to produce a concentrated urine.


2004 ◽  
Vol 287 (5) ◽  
pp. F878-F885 ◽  
Author(s):  
Ki-Hwan Han ◽  
Seung Kyoon Woo ◽  
Wan-Young Kim ◽  
Soo-Hyun Park ◽  
Jung-Ho Cha ◽  
...  

Tonicity-responsive enhancer binding protein (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 heat shock protein 70. To understand the role of TonEBP in the development of urinary concentrating ability, TonEBP expression during rat kidney development was investigated. In embryonic kidneys, TonEBP immunoreactivity was detected 16 days postcoitus 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, 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 sodium- myo-inositol cotransporter mRNA abundance. Thereafter, TonEBP expression in tubular profiles increased moderately. The 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 urine-concentrating ability.


1999 ◽  
Vol 277 (3) ◽  
pp. F437-F446 ◽  
Author(s):  
Noriyuki Miyata ◽  
Frank Park ◽  
Xiao Feng Li ◽  
Allen W. Cowley

ANG II contributes importantly to the regulation of renal vascular resistance, glomerular filtration, and tubular epithelial transport, yet there remains a paucity of information regarding the localization of the ANG II type 1 and 2 (AT1 and AT2) receptors within the rat kidney particularly within the vasculature. The present study was designed to localize the transcriptional and translational site(s) of AT1 and AT2 receptor (AT1R and AT2R, respectively) expression within the rat kidney. Using immunohistochemistry, we detected the AT1R translational sites throughout the kidney, with the strongest labeling found in the vasculature of the renal cortex and the proximal tubules of the outer medulla. The AT2R protein expression was found throughout the rat kidney, although there was little to no expression found in the glomerulus and medullary thick ascending limbs of Henle (TAL). Gene-specific primers were then designed to distinguish between the receptor subtypes within microdissected renal tubular and vascular segments using RT-PCR. AT1AR, AT1BR, and AT2R mRNA were found within the renal vasculature (afferent arterioles, arcuate artery, and outer medullary descending vasa recta). The mRNA for both the AT1R isoforms was also detected in the glomeruli and the renal tubules (proximal tubules, TAL, and collecting ducts); however, no AT2R mRNA was detected within the glomerulus and was inconsistently found within the medullary TAL (MTAL). Taken together, these data show that mRNA for the AT1R subtypes was located in all of the renal tubular and vascular segments. Evidence for AT2R mRNA was also found in all but two of the vascular and tubular segments, the MTAL, and the glomeruli. These results are consistent with the whole tissue immunohistochemically localized receptors.


2001 ◽  
Vol 12 (7) ◽  
pp. 1410-1421
Author(s):  
JUNG-HO CHA ◽  
YOUNG-HEE KIM ◽  
JU-YOUNG JUNG ◽  
KI-HWAN HAN ◽  
KIRSTEN M. MADSEN ◽  
...  

Abstract. In the developing rat kidney, there is no separation of the medulla into an outer and inner zone. At the time of birth, ascending limbs with immature distal tubule epithelium are present throughout the renal medulla, all loops of Henle resemble the short loop of adult animals, and there are no ascending thin limbs. It was demonstrated previously that immature thick ascending limbs in the renal papilla are transformed into ascending thin limbs by apoptotic deletion of cells and transformation of the remaining cells into a thin squamous epithelium. However, it is not known whether this is the only source of ascending thin limb cells or whether cell proliferation occurs in the segment undergoing transformation. This study was designed to address these questions and to identify sites of cell proliferation in the loop of Henle. Rat pups, 1, 3, 5, 7, and 14 d old, received a single injection of 5-bromo-2′-deoxyuridine (BrdU) 18 h before preservation of kidneys for immunohistochemistry. Thick ascending and descending limbs were identified by labeling with antibodies against the serotonin receptor, 5-HT1A, and aquaporin-1, respectively. Proliferating cells were identified with an antibody against BrdU. BrdU-positive cells in descending and ascending limbs of the loop of Henle were counted and expressed as percentages of the total number of aquaporin-1—positive and 5-HT1A—positive cells in the different segments. In the developing kidney, numerous BrdU-positive nuclei were observed in the nephrogenic zone. Outside of this location, BrdU-positive tubule cells were most prevalent in medullary rays in the inner cortex and in the outer medulla. BrdU-labeled cells were rare in the papillary portion of the loop of Henle and were not observed in the lower half of the papilla after 3 d of age. BrdU-labeled nuclei were not observed in segments undergoing transformation or in newly formed ascending thin limb epithelium. It was concluded that the growth zone for the loop of Henle is located around the corticomedullary junction, and the ascending thin limb is mainly, if not exclusively, derived from cells of the thick ascending limb.


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