1110: Increased Intercalated Versus Principal Cells in Inner Medullary Collecting Ducts in Human Stone Formers

2005 ◽  
Vol 173 (4S) ◽  
pp. 301-301
Author(s):  
Chung Kuang Su ◽  
Jonathan N. Rubenstein ◽  
Affonso H.L.A. Camargo ◽  
Stephen L. Gluck ◽  
Marshall L. Stoller
Keyword(s):  
Principal Cells ◽  
Stone Formers ◽  
Collecting Ducts

scholarly journals Integrin-β1 is required for the renal cystogenesis caused by ciliary defects

2020 ◽  
Vol 318 (5) ◽  
pp. F1306-F1312
Author(s):  
Miran Yoo ◽  
Laura M. C. Barisoni ◽  
Kyung Lee ◽  
G. Luca Gusella
Keyword(s):  
Inflammatory Infiltrate ◽  
Primary Cilia ◽  
Genetic Model ◽  
Renal Cysts ◽  
Intraflagellar Transport ◽  
The Other ◽  
Integrin Β1 ◽  
Principal Cells ◽  
Other Hand ◽  
Collecting Ducts

Defects in the function of primary cilia are commonly associated with the development of renal cysts. On the other hand, the intact cilium appears to contribute a cystogenic signal whose effectors remain unclear. As integrin-β1 is required for the cystogenesis caused by the deletion of the polycystin 1 gene, we asked whether it would be similarly important in the cystogenetic process caused by other ciliary defects. We addressed this question by investigating the effect of integrin-β1 deletion in a ciliopathy genetic model in which the Ift88 gene, a component of complex B of intraflagellar transport that is required for the proper assembly of cilia, is specifically ablated in principal cells of the collecting ducts. We showed that the renal cystogenesis caused by loss of Ift88 is prevented when integrin-β1 is simultaneously depleted. In parallel, pathogenetic manifestations of the disease, such as increased inflammatory infiltrate and fibrosis, were also significantly reduced. Overall, our data indicate that integrin-β1 is also required for the renal cystogenesis caused by ciliary defects and point to integrin-β1-controlled pathways as common drivers of the disease and as possible targets to interfere with the cystogenesis caused by ciliary defects.

Effect of dietary K+ and 75% nephrectomy on the morphology of principal cells in CCDs

1989 ◽  
Vol 256 (3) ◽  
pp. F387-F396
Author(s):  
R. K. Zalups
Keyword(s):  
Surface Density ◽  
Renal Mass ◽  
Basolateral Membrane ◽  
Inhibitory Effect ◽  
Potassium Depletion ◽  
Large Reduction ◽  
Factors Associated ◽  
Principal Cells ◽  
Marked Inhibitory Effect ◽  
Collecting Ducts

This investigation was carried out to determine the effect of potassium on the amplification of the basolateral membrane of principal cells in cortical collecting ducts (CCDs), which normally occurs after a large reduction of renal mass. Rats that underwent a 75% reduction of renal mass and were fed a diet deficient in potassium for 10 days after surgery had a lower concentration of potassium in the blood and excreted less potassium in the urine than either corresponding sham-operated (SO) rats or 75% nephrectomized (NPX) rats fed a normal-potassium diet. In the NPX rats fed the diet deficient in potassium, there was a marked inhibitory effect on the amplification of the basolateral membrane, which normally occurs in principal cells of CCDs after renal mass has been greatly reduced. In fact the surface density of the basolateral membrane, as well as the size of the principal cells in the animals fed the diet deficient in potassium were the same as those of principal cells in the SO rats fed the normal-potassium diet. Thus the present data show that the increase in cell size and the amplification of the basolateral membrane that occurs in principal cells after a 75% reduction of renal mass is inhibited by factors associated with potassium depletion.

scholarly journals Detection and localization of H+-K+-ATPase isoforms in human kidney

2001 ◽  
Vol 281 (4) ◽  
pp. F763-F768 ◽  
Author(s):  
Jeffrey A. Kraut ◽  
Kerstin G. Helander ◽  
Herbert F. Helander ◽  
Ngozi D. Iroezi ◽  
Elizabeth A. Marcus ◽  
...  
Keyword(s):  
Human Kidney ◽  
Renal Tissue ◽  
Intercalated Cells ◽  
Cytoplasmic Staining ◽  
Principal Cells ◽  
Medullary Tissue ◽  
Collecting Ducts ◽  
Light Staining ◽  
Immunohistochemical Studies ◽  
Detection And Localization

An H+-K+-ATPase contributes to hydrogen secretion and potassium reabsorption by the rat and rabbit collecting ducts. Transport of these ions appears to be accomplished by one or both of two isoforms of the H+-K+-ATPase, HKα1 and HKα2, because both isoforms are found in the collecting ducts and transport of hydrogen and potassium is attenuated by exposure to inhibitors of these transport proteins. To evaluate whether an H+-K+-ATPase is present in the human kidney, immunohistochemical studies were performed using normal human renal tissue probed with antibodies directed against epitopes of three of the known isoforms of the H+-K+-ATPase, HKα1, HKα2, and HKα4, and the V-type H+-ATPase. Cortical and medullary tissue probed with antibodies against HKα1 showed cytoplasmic staining of intercalated cells that was less intense than that observed in the parietal cells of normal rat stomach stained with the same antibody. Also, weak immunoreactivity was detected in principal cells of the human collecting ducts. Cortical and medullary tissue probed with antibodies directed against HKα4 revealed weak, diffuse staining of intercalated cells of the collecting ducts and occasional light staining of principal cells. Cortical and medullary tissue probed with antibodies directed against the H+-ATPase revealed staining of intercalated cells of the collecting ducts and some cells of the proximal convoluted tubules. By contrast, no discernible staining was noted with the use of the antibody against HKα2. These data indicate that HKα1 and HKα4 are present in the collecting ducts of the human kidney. In this location, these isoforms might contribute to hydrogen and potassium transport by the kidney.

scholarly journals Chymase Protein Expressed in Principal Cells of Inner Medullary Collecting Ducts in Diabetic Kidney Disease

2013 ◽  
Vol 27 (S1) ◽  
Author(s):  
Kirsten Ali Wood ◽  
Stephen M. Ford ◽  
Paul M. Berner ◽  
Nawazish Naqvi ◽  
Ahsan Husain ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Diabetic Kidney ◽  
Principal Cells ◽  
Collecting Ducts

scholarly journals Fluconazole Increases Osmotic Water Transport in Renal Collecting Duct through Effects on Aquaporin-2 Trafficking

2019 ◽  
Vol 30 (5) ◽  
pp. 795-810 ◽  
Author(s):  
Tanja Vukićević ◽  
Christian Hinze ◽  
Sandrine Baltzer ◽  
Nina Himmerkus ◽  
Catarina Quintanova ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Diabetes Insipidus ◽  
Nephrogenic Diabetes Insipidus ◽  
Collecting Duct ◽  
Urinary Output ◽  
Membrane Localization ◽  
Water Reabsorption ◽  
Principal Cells ◽  
Plasma Membrane Localization ◽  
Collecting Ducts

BackgroundArginine-vasopressin (AVP) binding to vasopressin V2 receptors promotes redistribution of the water channel aquaporin-2 (AQP2) from intracellular vesicles into the plasma membrane of renal collecting duct principal cells. This pathway fine-tunes renal water reabsorption and urinary concentration, and its perturbation is associated with diabetes insipidus. Previously, we identified the antimycotic drug fluconazole as a potential modulator of AQP2 localization.MethodsWe assessed the influence of fluconazole on AQP2 localization in vitro and in vivo as well as the drug's effects on AQP2 phosphorylation and RhoA (a small GTPase, which under resting conditions, maintains F-actin to block AQP2-bearing vesicles from reaching the plasma membrane). We also tested fluconazole's effects on water flow across epithelia of isolated mouse collecting ducts and on urine output in mice treated with tolvaptan, a VR2 blocker that causes a nephrogenic diabetes insipidus–like excessive loss of hypotonic urine.ResultsFluconazole increased plasma membrane localization of AQP2 in principal cells independent of AVP. It also led to an increased AQP2 abundance associated with alterations in phosphorylation status and ubiquitination as well as inhibition of RhoA. In isolated mouse collecting ducts, fluconazole increased transepithelial water reabsorption. In mice, fluconazole increased collecting duct AQP2 plasma membrane localization and reduced urinary output. Fluconazole also reduced urinary output in tolvaptan-treated mice.ConclusionsFluconazole promotes collecting duct AQP2 plasma membrane localization in the absence of AVP. Therefore, it might have utility in treating forms of diabetes insipidus (e.g., X-linked nephrogenic diabetes insipidus) in which the kidney responds inappropriately to AVP.

The actin-binding proteins adseverin and gelsolin are both highly expressed but differentially localized in kidney and intestine

1998 ◽  
Vol 111 (24) ◽  
pp. 3633-3643 ◽  
Author(s):  
A. Lueck ◽  
D. Brown ◽  
D.J. Kwiatkowski
Keyword(s):  
Cell Function ◽  
Immunoblot Analysis ◽  
Distal Convoluted Tubule ◽  
Actin Binding ◽  
Intercalated Cells ◽  
Principal Cells ◽  
Adult Kidney ◽  
Highly Sensitive ◽  
Collecting Ducts ◽  
High Level

To understand the distinct functions of the closely related actin-severing proteins adseverin and gelsolin, we examined the expression of these proteins in detail during mouse and human development using a new highly sensitive and specific set of antibody reagents. Immunoblot analysis demonstrated that adseverin was highly expressed in mouse kidney and intestine at all stages of development and in human fetal and adult kidney. In contrast and as reported previously, gelsolin was expressed much more widely in both murine and human tissues. Immunohistochemistry on murine kidney sections revealed a predominantly differential localization of adseverin and gelsolin. Adseverin was expressed in peripolar cells, thin limbs, thick ascending limbs, and principal cells of cortical and medullary collecting ducts where it was diffusely localized in the cytoplasm. Gelsolin was expressed in the distal convoluted tubule, intercalated cells and principal cells of cortical and medullary collecting ducts, and in ureter. In the distal convoluted tubule, gelsolin showed a diffuse distribution and in principal cells of collecting ducts a localization at the basolateral pole. In intercalated cells, gelsolin localization was heterogeneous, either at the apical pole or diffusely in the cytoplasm. In human fetal and adult kidney, adseverin was expressed only in collecting ducts whereas gelsolin was expressed in thick ascending limbs and collecting ducts. In mouse and human intestine adseverin was expressed in enterocytes with a gradient of increasing expression from the duodenum to the colon, and from the crypt to the villus. The observations indicate high level expression of adseverin in specific cells of the kidney and colon, and suggest a previously unrecognized function of adseverin in epithelial cell function.

Changes in cellular composition of kidney collecting duct cells in rats with lithium-induced NDI

2004 ◽  
Vol 286 (4) ◽  
pp. C952-C964 ◽  
Author(s):  
Birgitte Mønster Christensen ◽  
David Marples ◽  
Young-Hee Kim ◽  
Weidong Wang ◽  
Jørgen Frøkiær ◽  
...  
Keyword(s):  
Collecting Duct ◽  
Lithium Treatment ◽  
Intercalated Cells ◽  
Cellular Organization ◽  
Principal Cells ◽  
Duct Cells ◽  
Collecting Ducts ◽  
Collecting Duct Cells ◽  
Principal And Intercalated Cells ◽  
Double Immunolabeling

Lithium treatment for 4 wk caused severe polyuria, dramatic downregulation in aquaporin-2 (AQP-2) expression, and marked decrease in AQP-2 immunoreactivity with the appearance of a large number of cells without AQP-2 labeling in the collecting ducts after lithium treatment. Surprisingly, this was not all due to an increase in AQP-2-negative principal cells, because double immunolabeling revealed that the majority of the AQP-2-negative cells displayed [H+]ATPase labeling, which identified them as intercalated cells. Moreover, multiple [H+]ATPase-labeled cells were adjacent, which was never seen in control rats. Quantitation confirmed a significant decrease in the fraction of collecting duct cells that exhibited detectable AQP-2 labeling compared with control rats: in cortical collecting ducts, 40 ± 3.4 vs. 62 ± 1.8% of controls ( P < 0.05; n = 4) and in inner medullary collecting ducts, 58 ± 1.6 vs. 81 ± 1.3% of controls ( P < 0.05; n = 4). In parallel, a significant increase in the fraction of intercalated ([H+]ATPase-positive) cells was shown. Urine output, whole kidney AQP-2 expression, cellular organization, and the fractions of principal and intercalated cells in cortex and inner medulla returned to control levels after 4 wk on a lithium-free diet following 4 wk on a lithium-containing diet. In conclusion, lithium treatment not only decreased AQP-2 expression, but dramatically and reversibly reduced the fraction of principal cells and altered the cellular organization in collecting ducts. These effects are likely to be important in lithium-induced nephrogenic diabetes insipidus.

scholarly journals ENaC activity is increased in isolated, split-open cortical collecting ducts from protein kinase Cα knockout mice

2014 ◽  
Vol 306 (3) ◽  
pp. F309-F320 ◽  
Author(s):  
Hui-Fang Bao ◽  
Tiffany L. Thai ◽  
Qiang Yue ◽  
He-Ping Ma ◽  
Amity F. Eaton ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Knockout Mice ◽  
Membrane Localization ◽  
Na Channel ◽  
Renal Tubules ◽  
Wild Type ◽  
Open Probability ◽  
Principal Cells ◽  
Collecting Ducts

The epithelial Na channel (ENaC) is negatively regulated by protein kinase C (PKC) as shown using PKC activators in a cell culture model. To determine whether PKCα influences ENaC activity in vivo, we examined the regulation of ENaC in renal tubules from PKCα−/− mice. Cortical collecting ducts were dissected and split open, and the exposed principal cells were subjected to cell-attached patch clamp. In the absence of PKCα, the open probability ( Po) of ENaC was increased three-fold vs. wild-type SV129 mice (0.52 ± 0.04 vs. 0.17 ± 0.02). The number of channels per patch was also increased. Using confocal microscopy, we observed an increase in membrane localization of α-, β-, and γ-subunits of ENaC in principal cells in the cortical collecting ducts of PKCα−/− mice compared with wild-type mice. To confirm this increase, one kidney from each animal was perfused with biotin, and membrane protein was pulled down with streptavidin. The nonbiotinylated kidney was used to assess total protein. While total ENaC protein did not change in PKCα−/− mice, membrane localization of all the ENaC subunits was increased. The increase in membrane ENaC could be explained by the observation that ERK1/2 phosphorylation was decreased in the knockout mice. These results imply a reduction in ENaC membrane accumulation and Po by PKCα in vivo. The PKC-mediated increase in ENaC activity was associated with an increase in blood pressure in knockout mice fed a high-salt diet.

scholarly journals Endogenous Notch Signaling in Adult Kidneys Maintains Segment-Specific Epithelial Cell Types of the Distal Tubules and Collecting Ducts to Ensure Water Homeostasis

2018 ◽  
Vol 30 (1) ◽  
pp. 110-126 ◽  
Author(s):  
Malini Mukherjee ◽  
Jennifer deRiso ◽  
Karla Otterpohl ◽  
Ishara Ratnayake ◽  
Divya Kota ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Notch Signaling ◽  
Kidney Development ◽  
Collecting Duct ◽  
Lithium Treatment ◽  
Cell Types ◽  
Intercalated Cells ◽  
Principal Cells ◽  
Adult Kidney ◽  
Collecting Ducts

BackgroundNotch signaling is required during kidney development for nephron formation and principal cell fate selection within the collecting ducts. Whether Notch signaling is required in the adult kidney to maintain epithelial diversity, or whether its loss can trigger principal cell transdifferentiation (which could explain acquired diabetes insipidus in patients receiving lithium) is unclear.MethodsTo investigate whether loss of Notch signaling can trigger principal cells to lose their identity, we genetically inactivated Notch1 and Notch2, inactivated the Notch signaling target Hes1, or induced expression of a Notch signaling inhibitor in all of the nephron segments and collecting ducts in mice after kidney development. We examined renal function and cell type composition of control littermates and mice with conditional Notch signaling inactivation in adult renal epithelia. In addition, we traced the fate of genetically labeled adult kidney collecting duct principal cells after Hes1 inactivation or lithium treatment.ResultsNotch signaling was required for maintenance of Aqp2-expressing cells in distal nephron and collecting duct segments in adult kidneys. Fate tracing revealed mature principal cells in the inner stripe of the outer medulla converted to intercalated cells after genetic inactivation of Hes1 and, to a lesser extent, lithium treatment. Hes1 ensured repression of Foxi1 to prevent the intercalated cell program from turning on in mature Aqp2+ cell types.ConclusionsNotch signaling viaHes1 regulates maintenance of mature renal epithelial cell states. Loss of Notch signaling or use of lithium can trigger transdifferentiation of mature principal cells to intercalated cells in adult kidneys.

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