Patterns of differentiation of renin lineage cells during nephrogenesis

2021 ◽  
Author(s):  
Friederike Kessel ◽  
Anne Steglich ◽  
Linda Hickmann ◽  
Ricardo Lira-Martinez ◽  
Michael Gerlach ◽  
...  
Keyword(s):  
De Novo ◽  
Mesangial Cells ◽  
Collecting Duct ◽  
Cell Types ◽  
Proliferation Rate ◽  
Metanephric Mesenchyme ◽  
Embryonic Origin ◽  
Cap Mesenchyme ◽  
Developing Kidney ◽  
Renal Vascular

Developmentally heterogeneous renin expressing cells serve as progenitors for mural, glomerular and tubular cells during nephrogenesis and are collectively termed renin lineage cells (RLCs). In this study, we quantified different renal vascular and tubular cell types based on specific markers, assessed proliferation, and de-novo differentiation in the RLC population. We used kidney sections of mRenCre-mT/mG mice throughout nephrogenesis. Marker positivity was evaluated in whole digitalized sections. At embryonic day 16, RLCs appeared in the developing kidney, and expression of all stained markers in RLCs was observed. The proliferation rate of RLCs did not differ from the proliferation rate of non-RLCs. The RLCs expanded mainly by de-novo differentiation (neogenesis). The fractions of RLCs originating from the stromal progenitors of the metanephric mesenchyme (renin producing cells, vascular smooth muscle cells, mesangial cells) decreased during nephrogenesis. In contrast, aquaporin 2 positive RLCs in the collecting duct system that embryonically emerges almost exclusively from the ureteric bud, expanded postpartum. The cubilin positive RLC fraction in the proximal tubule, deriving from the cap mesenchyme, remained constant. During nephrogenesis, RLCs were continuously detectable in the vascular and tubular compartments of the kidney. Therein, various patterns of RLC differentiation that depend on the embryonic origin of the cells were identified.

scholarly journals Single-cell RNA sequencing reveals differential cell cycle activity in key cell populations during nephrogenesis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Abha S. Bais ◽  
Débora M. Cerqueira ◽  
Andrew Clugston ◽  
Andrew J. Bodnar ◽  
Jacqueline Ho ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Single Cell ◽  
Molecular Mechanisms ◽  
Kidney Development ◽  
Collecting Duct ◽  
Cell Types ◽  
Nephron Progenitors ◽  
Developing Kidney ◽  
Distal Tubules ◽  
Cycle Regulation

AbstractThe kidney is a complex organ composed of more than 30 terminally differentiated cell types that all are required to perform its numerous homeostatic functions. Defects in kidney development are a significant cause of chronic kidney disease in children, which can lead to kidney failure that can only be treated by transplant or dialysis. A better understanding of molecular mechanisms that drive kidney development is important for designing strategies to enhance renal repair and regeneration. In this study, we profiled gene expression in the developing mouse kidney at embryonic day 14.5 at single-cell resolution. Consistent with previous studies, clusters with distinct transcriptional signatures clearly identify major compartments and cell types of the developing kidney. Cell cycle activity distinguishes between the “primed” and “self-renewing” sub-populations of nephron progenitors, with increased expression of the cell cycle-related genes Birc5, Cdca3, Smc2 and Smc4 in “primed” nephron progenitors. In addition, augmented expression of cell cycle related genes Birc5, Cks2, Ccnb1, Ccnd1 and Tuba1a/b was detected in immature distal tubules, suggesting cell cycle regulation may be required for early events of nephron patterning and tubular fusion between the distal nephron and collecting duct epithelia.

Prostaglandin transporter PGT is expressed in cell types that synthesize and release prostanoids

2002 ◽  
Vol 282 (6) ◽  
pp. F1103-F1110 ◽  
Author(s):  
Yi Bao ◽  
Michael L. Pucci ◽  
Brenda S. Chan ◽  
Run Lu ◽  
Shigekazu Ito ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Mesangial Cells ◽  
Collecting Duct ◽  
Rat Kidney ◽  
Cell Types ◽  
Proximal Tubules ◽  
Surface Epithelium ◽  
Extracellular Loop ◽  
Insight Into ◽  
Rat Platelets

PGT is a broadly expressed transporter of prostaglandins (PGs) and thromboxane that is energetically poised to take up prostanoids across the plasma membrane. To gain insight into the function of PGT, we generated mouse monoclonal antibody 20 against a portion of putative extracellular loop 5 of rat PGT. Immunoblots of endogenous PGT in rat kidney revealed a 65-kDa protein in a zonal pattern corresponding to PG synthesis rates (papilla ≅ medulla > cortex). Immunocytochemically, PGT in rat kidneys was expressed in glomerular endothelial and mesangial cells, arteriolar endothelial and muscularis cells, principal cells of the collecting duct, medullary interstitial cells, medullary vasa rectae endothelia, and papillary surface epithelium. Proximal tubules, which are known to take up and metabolize PGs, were negative. Immunoblotting and immunocytochemistry revealed that rat platelets also express abundant PGT. Coexpression of the PG synthesis apparatus (cyclooxygenase) and PGT by the same cell suggests that prostanoids may undergo release and reuptake.

Endothelin synthesis by rabbit renal tubule cells

1991 ◽  
Vol 261 (2) ◽  
pp. F221-F226 ◽  
Author(s):  
D. E. Kohan
Keyword(s):  
High Performance ◽  
Renal Tubule ◽  
De Novo ◽  
Collecting Duct ◽  
Cell Types ◽  
Phospholipid Metabolism ◽  
Thick Ascending Limb ◽  
Medullary Collecting Duct ◽  
Tubule Cells ◽  
Endothelin 3

Endothelins regulate nephron sodium and water transport, prostaglandin E2 (PGE2) synthesis, and phospholipid metabolism. Recent studies suggest that renal tubule cells synthesize endothelins. To determine which nephron sites have such potential, endothelin production by cells derived from different nephron segments was examined. Immunoreactive endothelin 1 (ET-1) and endothelin 3 (ET-3) were measured in supernatants of cultured rabbit proximal tubule (PT), medullary thick ascending limb (MTAL), cortical collecting tubule (CCT), and inner medullary collecting duct (IMCD) cells. All cell types released immunoreactive ET-1 and ET-3. However, the amounts of endothelin produced differed as follows: IMCD greater than MTAL greater than CCT much greater than PT for ET-1 and IMCD greater than MTAL = PT = CCT for ET-3; in all cases ET-1 much greater than ET-3. To confirm de novo ET-3 synthesis, IMCD cells were labeled with [35S]cysteine, and the supernatant was immunoprecipitated with anti-ET-3 antibody. Sample and standard ET-3 eluted at identical positions on high-performance liquid chromatographs, confirming de novo synthesis of ET-3 by cultured IMCD cells. These data raise the possibility of an important functional role for nephron-derived endothelin and, in particular, endothelin produced by tubule cells in the medulla.

scholarly journals Differential renal distribution of NHERF isoforms and their colocalization with NHE3, ezrin, and ROMK

2001 ◽  
Vol 280 (1) ◽  
pp. C192-C198 ◽  
Author(s):  
James B. Wade ◽  
Paul A. Welling ◽  
Mark Donowitz ◽  
Shirish Shenolikar ◽  
Edward J. Weinman
Keyword(s):  
Proximal Tubule ◽  
Collecting Duct ◽  
Rat Kidney ◽  
Cell Types ◽  
Inhibitory Effect ◽  
Striking Difference ◽  
Proximal Tubule Cells ◽  
Signaling Complex ◽  
Renal Vascular ◽  
Different Cell Types

Na+/H+ exchanger regulatory factor (NHERF) and NHERF2 are PDZ motif proteins that mediate the inhibitory effect of cAMP on Na+/H+ exchanger 3 (NHE3) by facilitating the formation of a multiprotein signaling complex. With the use of antibodies specific for NHERF and NHERF2, immunocytochemical analysis of rat kidney was undertaken to determine the nephron distribution of both proteins and their colocalization with other transporters and with ezrin. NHERF was most abundant in apical membrane of proximal tubule cells, where it colocalized with ezrin and NHE3. NHERF2 was detected in the glomerulus and in other renal vascular structures. In addition, NHERF2 was strongly expressed in collecting duct principal cells, where it colocalized with ROMK. These results indicate a striking difference in the nephron distribution of NHERF and NHERF2 and suggests NHERF is most likely to be the relevant biological regulator of NHE3 in the proximal tubule, while NHERF2 may interact with ROMK or other targets in the collecting duct. The finding that NHERF isoforms occur in different cell types suggests that NHERF and NHERF2 may subserve different functions in the kidney.

Regulation of mesangial cell hexokinase activity by PKC and the classic MAPK pathway

1999 ◽  
Vol 277 (5) ◽  
pp. F742-F749 ◽  
Author(s):  
R. Brooks Robey ◽  
Jianfei Ma ◽  
Anna V. P. Santos
Keyword(s):  
Time Course ◽  
Phorbol Esters ◽  
Mesangial Cell ◽  
De Novo ◽  
Mesangial Cells ◽  
Mapk Pathway ◽  
Lactate Production ◽  
Cell Types ◽  
Functional Coupling ◽  
Dependent Manner

Phorbol esters increase glucose (Glc) uptake and utilization in a variety of cell types, and, in some cells, these changes have been attributed to increased Glc phosphorylation and better functional coupling of hexokinases (HKs) to facilitative Glc transporters. Phorbol esters are potent mesangial cell mitogens, but their effects on HK-catalyzed Glc phosphorylation and metabolism are unknown. When examined in murine mesangial cells, active, but not inactive, phorbol esters increased HK activity in a time- and dose-dependent manner. Maximal induction of HK activity at 12–24 h was accompanied by parallel increases in both Glc utilization and lactate production and was blocked by the specific MEK1/2 inhibitor PD-98059 (IC50∼3 μM). This effect involved early activation of protein kinase C (PKC), MEK1/2, and ERK1/2, and the prolonged time course of subsequent HK induction was attributable, in part, to requirements for ongoing gene transcription and de novo protein synthesis. Mesangial cell HK activity thus exhibits novel regulatory behavior involving both PKC and classic MAPK pathway activation, suggesting specific mechanisms whereby PKC activation may influence Glc metabolism.

scholarly journals Embryonic Kidney Development, Stem Cells and the Origin of Wilms Tumor

Genes ◽  
2021 ◽  
Vol 12 (2) ◽  
pp. 318
Author(s):  
Hao Li ◽  
Peter Hohenstein ◽  
Satu Kuure
Keyword(s):  
Stem Cells ◽  
Connective Tissue ◽  
Kidney Development ◽  
Mesangial Cells ◽  
Wilms Tumor ◽  
Collecting Duct ◽  
Duct System ◽  
Hematopoietic System ◽  
Developing Kidney ◽  
Nephrogenic Rests

The adult mammalian kidney is a poorly regenerating organ that lacks the stem cells that could replenish functional homeostasis similarly to, e.g., skin or the hematopoietic system. Unlike a mature kidney, the embryonic kidney hosts at least three types of lineage-specific stem cells that give rise to (a) a ureter and collecting duct system, (b) nephrons, and (c) mesangial cells together with connective tissue of the stroma. Extensive interest has been raised towards these embryonic progenitor cells, which are normally lost before birth in humans but remain part of the undifferentiated nephrogenic rests in the pediatric renal cancer Wilms tumor. Here, we discuss the current understanding of kidney-specific embryonic progenitor regulation in the innate environment of the developing kidney and the types of disruptions in their balanced regulation that lead to the formation of Wilms tumor.

scholarly journals Σπειραματικά επίπεδα και προέλευση του παράγοντα ενεργοποίησης των αιμοπεταλίων (PAF) στην πειραματική σπειραματονεφρίτιδα

1990 ◽  
Author(s):  
Αντώνιος Ζάγκλης
Keyword(s):  
De Novo ◽  
Mesangial Cells ◽  
Rat Kidney ◽  
Platelet Activating Factor ◽  
Cell Types ◽  
Transferase Activity ◽  
Polymorphonuclear Leucocytes ◽  
Alkyl Ether ◽  
Nephrotoxic Serum Nephritis ◽  
Dependent Model

The renal glomerulus and its various cell types (i.e. mesangial cells, endothelial cells) have been shown to synthesize compounds with autacoid and proinflammatory effects. [97,98] The spectrum of proinflammatory compounds of glomerular origin has recently expanded to include the alkyl ether glycerophospholipids, including 1-O-alkyl-2- acetyl-sn- glycero-3- phosphorylcholine, which is structurally identical with platelet activating factor (PAF).This compound can induce platelet and neutrophil aggregation and chemokinesis, vasodilation, increased vascular permeability and stimulation of eicosanoid production. We have demonstrated that PAF can be both synthesized and degraded in isolated glomeruli and in mesangial cells, [7,99] the latter being also capable of de novo synthesis of PAF precursors. Recent observations indicate that PAF receptor antagonism ameliorates glomerular inflammation in rabbit nephrotoxic serum nephritis, as well as the glomerular inflammatory injury induced by in situ formation of immune complexes in the rat kidney with experimental passive reverse Arthus reaction. [100,101] The present study was undertaken in order to assess the levels and cellular sources of glomerular PAF in glomeruli isolated from rats with: 1) Nephrotoxic serum nephritis, an infiltrative and complement dependent model of immune injury and 2) passive Heymann nephritis a non- infiltrative but complement dependent model. The role of complement, platelets and polymorphonuclear leucocytes was assessed. The observation that mesangial cells is the main source of PAF production in the rat glomerulus, prompted the assessment of the effect of various inflammatory mediators on the acetyl-transferase activity of the mesangial cells. […]

scholarly journals Recognition of the laminin E8 cell-binding site by an integrin possessing the alpha 6 subunit is essential for epithelial polarization in developing kidney tubules.

1990 ◽  
Vol 111 (3) ◽  
pp. 1265-1273 ◽  
Author(s):  
L Sorokin ◽  
A Sonnenberg ◽  
M Aumailley ◽  
R Timpl ◽  
P Ekblom
Keyword(s):  
Epithelial Cells ◽  
Binding Site ◽  
Apical Cell ◽  
Cell Types ◽  
Metanephric Mesenchyme ◽  
Kidney Tubule ◽  
Cell Binding ◽  
Developing Kidney ◽  
A Chain ◽  
Integrin Alpha 6

It has been previously shown that A-chain and domain(E8)-specific antibodies to laminin that inhibit cell adhesion also interfere with the establishment of epithelial cell polarity during kidney tubule development (Klein, G., M. Langegger, R. Timpl, and P. Ekblom. 1988. Cell. 55:331-341). A monoclonal antibody specific for the integrin alpha 6 subunit, which selectively blocks cell binding to E8, was used to study the receptors involved. Immunofluorescence staining of embryonic kidneys and of organ cultures of metanephric mesenchyme demonstrated coappearance of the integrin alpha 6 subunit and the laminin A-chain in regions where nonpolarized mesenchymal cells convert into polarized epithelial cells. Both epitopes showed marked colocalization in basal areas of tubules, while an exclusive immunostaining for alpha 6 was observed in lateral and apical cell surfaces of the tubular epithelial cells. Organ culture studies demonstrated a consistent inhibition of kidney epithelium development by antibodies against the alpha 6 subunit. The data suggest that the recognition of E8 cell-binding site of laminin by a specific integrin is crucial for the formation of kidney tubule epithelium from undifferentiated mesenchymal stem cells. In some other cell types (endothelium, some ureter cells) an exclusive expression of alpha 6 with no apparent colocalization of laminin A-chain in the corresponding basement membrane was seen. Thus, in these cells, integrins possessing the alpha 6 subunit may bind to laminin isoforms that differ from those synthesized by developing tubules.

scholarly journals Single cell RNA sequencing reveals differential cell cycle activity in key cell populations during nephrogenesis

2020 ◽  
Author(s):  
Abha S. Bais ◽  
Débora M. Cerqueira ◽  
Andrew Clugston ◽  
Jacqueline Ho ◽  
Dennis Kostka
Keyword(s):  
Cell Cycle ◽  
Single Cell ◽  
Molecular Mechanisms ◽  
Kidney Development ◽  
Collecting Duct ◽  
Cell Types ◽  
Ureteric Bud ◽  
Nephron Progenitors ◽  
Developing Kidney ◽  
Distal Tubules

ABSTRACTThe kidney is a complex organ composed of more than 30 terminally differentiated cell types that all are required to perform its numerous homeostatic functions. Defects in kidney development are a significant cause of chronic kidney disease in children, which can lead to kidney failure that can only be treated by transplant or dialysis. A better understanding of molecular mechanisms that drive kidney development is important for designing strategies to enhance renal repair and regeneration. In this study, we profiled gene expression in the developing mouse kidney at embryonic day 14.5 at single cell resolution. Consistent with previous studies, clusters with distinct transcriptional signatures clearly identify major compartments and cell types of the developing kidney. Cell cycle activity distinguishes between the “primed” and “self-renewing” sub-populations of nephron progenitors, with increased expression of the cell cycle related genes Birc5, Cdca3, Smc2 and Smc4 in “primed” nephron progenitors. Augmented Birc5 expression was also detected in immature distal tubules and a sub-set of ureteric bud cells, suggesting that Birc5 might be a novel key molecule required for early events of nephron patterning and tubular fusion between the distal nephron and the collecting duct epithelia.

Key enzymes for renal prostaglandin synthesis: site-specific expression in rodent kidney (rat, mouse)

2003 ◽  
Vol 285 (1) ◽  
pp. F19-F32 ◽  
Author(s):  
Valentina Câmpean ◽  
Franziska Theilig ◽  
Alex Paliege ◽  
Matthew Breyer ◽  
Sebastian Bachmann
Keyword(s):  
Mesangial Cells ◽  
Collecting Duct ◽  
Juxtaglomerular Apparatus ◽  
Cell Types ◽  
Arachidonic Acid Metabolism ◽  
Antigen Retrieval ◽  
Specific Expression ◽  
Key Enzymes ◽  
Cox 2 ◽  
Cox 1

Prostanoids derived from endogenous cylooxygenase (COX)-mediated arachidonic acid metabolism play important roles in the maintenance of renal blood flow and salt and water homeostasis. The relative importance of COX-1 and COX-2 isoforms is under active investigation. We have performed a comprehensive histochemical analysis by comparing rat and mouse kidneys for cellular and subcellular localization of COX-1 and -2 and microsomal-type PGE synthase (PGES), the rate-limiting biosynthetic enzyme in PGE2 synthesis. A choice of different sera was compared, and the results were confirmed by antigen-retrieval techniques, in situ hybridization, RT-PCR, and the use of COX knockout mice. In the glomerulus, significant COX-1 expression was detected in a subset of mesangial cells. Along the renal tubule, the known COX-2 expression in cTAL and macula densa was paralleled by PGES staining. In the terminal distal convoluted tubule, connecting tubule, and cortical and medullary collecting ducts, a significant COX-1 signal was colocalized with PGES; COX-2 was not found in these sites. Intercalated cells were generally negative. Cortical fibroblasts were COX-1 and PGES positive in mice, whereas in rats only PGES could be reliably detected. Lipid-laden interstitial cells of the inner medulla were COX-1, -2, and PGES positive. Vascular smooth muscle cells were not stained. The present data support prominent functions of renal prostanoids, predominantly PGE2, by defining expression sites of the key enzymes for their biosynthesis in the rat and mouse. Results define the renal cell types involved in prostaglandin autacoid functions within spatially restricted sites such as the juxtaglomerular apparatus, mesangium, distal convolutions and collecting duct, and in compartments of the renal interstitium.

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