Demonstration of prostaglandin synthesis in collecting duct cells and other cell types of the rabbit renal medulla

1977 ◽  
Vol 14 (4) ◽  
pp. 729-744 ◽  
Author(s):  
Sven-Olof Bohman
Keyword(s):  
Collecting Duct ◽  
Renal Medulla ◽  
Cell Types ◽  
Prostaglandin Synthesis ◽  
Duct Cells ◽  
Collecting Duct Cells

scholarly journals Transcriptomes of major renal collecting duct cell types in mouse identified by single-cell RNA-seq

2017 ◽  
Vol 114 (46) ◽  
pp. E9989-E9998 ◽  
Author(s):  
Lihe Chen ◽  
Jae Wook Lee ◽  
Chung-Lin Chou ◽  
Anil V. Nair ◽  
Maria A. Battistone ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Surface ◽  
Single Cell ◽  
Collecting Duct ◽  
Extracellular Fluid ◽  
Cell Types ◽  
Rna Seq ◽  
Duct Cells ◽  
Collecting Duct Cells ◽  
Renal Collecting Duct

Prior RNA sequencing (RNA-seq) studies have identified complete transcriptomes for most renal epithelial cell types. The exceptions are the cell types that make up the renal collecting duct, namely intercalated cells (ICs) and principal cells (PCs), which account for only a small fraction of the kidney mass, but play critical physiological roles in the regulation of blood pressure, extracellular fluid volume, and extracellular fluid composition. To enrich these cell types, we used FACS that employed well-established lectin cell surface markers for PCs and type B ICs, as well as a newly identified cell surface marker for type A ICs, c-Kit. Single-cell RNA-seq using the IC- and PC-enriched populations as input enabled identification of complete transcriptomes of A-ICs, B-ICs, and PCs. The data were used to create a freely accessible online gene-expression database for collecting duct cells. This database allowed identification of genes that are selectively expressed in each cell type, including cell-surface receptors, transcription factors, transporters, and secreted proteins. The analysis also identified a small fraction of hybrid cells expressing aquaporin-2 and anion exchanger 1 or pendrin transcripts. In many cases, mRNAs for receptors and their ligands were identified in different cells (e.g., Notch2 chiefly in PCs vs. Jag1 chiefly in ICs), suggesting signaling cross-talk among the three cell types. The identified patterns of gene expression among the three types of collecting duct cells provide a foundation for understanding physiological regulation and pathophysiology in the renal collecting duct.

Abstract 408: Hyperglycemia Increases the Prorenin Receptor in the Plasma Membrane of Collecting Duct Cells in Rats with Type 1 Diabetes Mellitus

Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Minolfa C Prieto ◽  
Danielle Y Arita ◽  
Camille T Bourgeois ◽  
Ryousuke Satou
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Collecting Duct ◽  
Renal Medulla ◽  
Ang Ii ◽  
Duct Cells ◽  
Prorenin Receptor ◽  
Collecting Duct Cells ◽  
Tubulointerstitial Inflammation

In type 1 diabetes mellitus (T1DM) there is increased prorenin secretion by the principal cells of the collecting duct. Binding of prorenin to prorenin receptor (PRR) on intercalated cells increases its catalytic activity, increases local angiotensin (Ang) II formation, and stimulates intracellular MAPK signaling responsible for inflammation and tissue fibrosis. Thus, changes in the amount of membrane bound PRR may be a key factor in stimulating these pathways. However, it has not been established that activation of PRR in the collecting duct contributes to increased intrarenal Ang II and tubulointerstitial inflammation via stimulation of inflammatory pathways including transforming growth factor-beta (TGF-β). This study tested the hypothesis that hyperglycemia increases the PRR abundance at the plasma membrane (PM) in the collecting duct cells, thus allowing greater capability to be activated by locally produced prorenin. Streptozotocin (STZ; 60 mg/kg; ip single dose) was used to induce T1DM in Sprague-Dawley rats (N=10) and compared to control rats (N=8). After 7-days induction, STZ-rats showed plasma glucose levels of 428±13 vs. 138±9 mg/dL and insulin of 0.05±0.02 vs. 2.4±0.6 ng/mL, compared to control. Although PRR transcript in the renal medulla were not different between groups; PRR localized predominantly on the apical aspects of collecting duct cells in STZ-induced rats; while in controls it was primarily found intracellularlly. These changes were accompanied by greater levels of active renin and Ang II in the urine and increased TGF-β mRNA levels in the renal medulla of STZ-rats (Renin: 186± 34 vs. 6± 3 ng Ang I/mL/h; P<0.01; Ang II: 884± 147 vs. 42± 14 fmol/h; P<0.05; TGF-β: 1.22 ± 0.06 vs. 0.97 ± 0.03 mRNA ratio; P<0.01). To further assess if hyperglycemia induced in vitro PRR trafficking alterations, collecting duct M-1 cells were treated with normal glucose (NG; 1mM glucose + 1 mM mannitol) and high glucose (HG; 4mM) for 5, 60, and 360 min. PRR protein levels were higher in the PM fractions in cells treated with HG, compared to cells treated with NG. Thus, hyperglycemia increases PRR abundance in the PM of the collecting duct and stimulates TGF-β synthesis in the renal medulla which may underlie the development of tubulointerstitial inflammation.

scholarly journals Pax2 and Pax8 Proteins Regulate Urea Transporters and Aquaporins to Control Urine Concentration in the Adult Kidney

2020 ◽  
Vol 31 (6) ◽  
pp. 1212-1225 ◽  
Author(s):  
Ann M. Laszczyk ◽  
Atsuko Y. Higashi ◽  
Sanjeevkumar R. Patel ◽  
Craig N. Johnson ◽  
Abdul Soofi ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Target Genes ◽  
Collecting Duct ◽  
Expression Patterns ◽  
Renal Medulla ◽  
Urine Concentration ◽  
Renal Epithelia ◽  
Duct Cells ◽  
Collecting Duct Cells ◽  
Collecting Tubules

BackgroundAs the glomerular filtrate passes through the nephron and into the renal medulla, electrolytes, water, and urea are reabsorbed through the concerted actions of solute carrier channels and aquaporins at various positions along the nephron and in the outer and inner medulla. Proliferating stem cells expressing the nuclear transcription factor Pax2 give rise to renal epithelial cells. Pax2 expression ends once the epithelial cells differentiate into mature proximal and distal tubules, whereas expression of the related Pax8 protein continues. The collecting tubules and renal medulla are derived from Pax2-positive ureteric bud epithelia that continue to express Pax2 and Pax8 in adult kidneys. Despite the crucial role of Pax2 in renal development, functions for Pax2 or Pax8 in adult renal epithelia have not been established.MethodsTo examine the roles of Pax2 and Pax8 in the adult mouse kidney, we deleted either Pax2, Pax8, or both genes in adult mice and examined the resulting phenotypes and changes in gene expression patterns. We also explored the mechanism of Pax8-mediated activation of potential target genes in inner medullary collecting duct cells.ResultsMice with induced deletions of both Pax2 and Pax8 exhibit severe polyuria that can be attributed to significant changes in the expression of solute carriers, such as the urea transporters encoded by Slc14a2, as well as aquaporins within the inner and outer medulla. Furthermore, Pax8 expression is induced by high-salt levels in collecting duct cells and activates the Slc14a2 gene by recruiting a histone methyltransferase complex to the promoter.ConclusionsThese data reveal novel functions for Pax proteins in adult renal epithelia that are essential for retaining water and concentrating urine.

scholarly journals Gender-Dependent Phenotype in Polycystic Kidney Disease Is Determined by Differential Intracellular Ca2+ Signals

2021 ◽  
Vol 22 (11) ◽  
pp. 6019
Author(s):  
Khaoula Talbi ◽  
Inês Cabrita ◽  
Rainer Schreiber ◽  
Karl Kunzelmann
Keyword(s):  
Cell Proliferation ◽  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Collecting Duct ◽  
Primary Cells ◽  
Loss Of Function ◽  
Polycystic Kidney ◽  
Chloride Currents ◽  
Duct Cells ◽  
Collecting Duct Cells

Autosomal dominant polycystic kidney disease (ADPKD) is caused by loss of function of PKD1 (polycystin 1) or PKD2 (polycystin 2). The Ca2+-activated Cl− channel TMEM16A has a central role in ADPKD. Expression and function of TMEM16A is upregulated in ADPKD which causes enhanced intracellular Ca2+ signaling, cell proliferation, and ion secretion. We analyzed kidneys from Pkd1 knockout mice and found a more pronounced phenotype in males compared to females, despite similar levels of expression for renal tubular TMEM16A. Cell proliferation, which is known to be enhanced with loss of Pkd1−/−, was larger in male when compared to female Pkd1−/− cells. This was paralleled by higher basal intracellular Ca2+ concentrations in primary renal epithelial cells isolated from Pkd1−/− males. The results suggest enhanced intracellular Ca2+ levels contributing to augmented cell proliferation and cyst development in male kidneys. Enhanced resting Ca2+ also caused larger basal chloride currents in male primary cells, as detected in patch clamp recordings. Incubation of mouse primary cells, mCCDcl1 collecting duct cells or M1 collecting duct cells with dihydrotestosterone (DHT) enhanced basal Ca2+ levels and increased basal and ATP-stimulated TMEM16A chloride currents. Taken together, the more severe cystic phenotype in males is likely to be caused by enhanced cell proliferation, possibly due to enhanced basal and ATP-induced intracellular Ca2+ levels, leading to enhanced TMEM16A currents. Augmented Ca2+ signaling is possibly due to enhanced expression of Ca2+ transporting/regulating proteins.

Whole cell and unitary amiloride-sensitive sodium currents in M-1 mouse cortical collecting duct cells

1996 ◽  
Vol 270 (4) ◽  
pp. C998-C1010 ◽  
Author(s):  
M. L. Chalfant ◽  
T. G. O'Brien ◽  
M. M. Civan
Keyword(s):  
Collecting Duct ◽  
Cell Permeability ◽  
Na Channel ◽  
Na Channels ◽  
Cortical Collecting Duct ◽  
Ionic Selectivity ◽  
Whole Cell ◽  
Duct Cells ◽  
Excised Patches ◽  
Collecting Duct Cells

Amiloride-sensitive whole cell currents have been reported in M-1 mouse cortical collecting duct cells (Korbmacher et al., J. Gen. Physiol. 102: 761-793, 1993). We have confirmed that amiloride inhibits the whole cell currents but not necessarily the measured whole cell currents. Anomalous responses were eliminated by removing external Na+ and/or introducing paraepithelial shunts. The amiloride-sensitive whole cell currents displayed Goldman rectification. The ionic selectivity sequence of the amiloride-sensitive conductance was Li+ > Na+ >> K+. Growth of M-1 cells on permeable supports increased the amiloride-sensitive whole cell permeability, compared with cells grown on plastic. Single amiloride-sensitive channels were observed, which conformed to the highly selective low-conductance amiloride-sensitive class [Na(5)] of epithelial Na+ channels. Hypotonic pretreatment markedly slowed run-down of channel activity. The gating of the M-1 Na+ channel in excised patches was complex. Open- and closed-state dwell-time distributions from patches that display one operative channel were best described with two or more exponential terms each. We conclude that 1) study of M-1 whole cell Na+ currents is facilitated by reducing the transepithelial potential to zero, 2) these M-1 currents reflect the operation of Na(5) channels, and 3) the Na+ channels display complex kinetics, involving > or = 2 open and > or = 2 closed states.

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