Uriniferous Tubule: Structural and Functional Organization

Christensen, Erik; Wagner, Carsten A.; Kaissling, Brigitte

doi:10.1002/cphy.c100073

Cited by 56 publications

(72 citation statements)

References 621 publications

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“…The mosaic pattern was seen in all nephrons studied and is probably a developmental feature, and it is difficult to see any functional implications. This mosaic pattern may be similar to the features seen, e.g., at the CNT with a mixture of CNT cells, principal cells, and intercalated cells, as recently reviewed by Christensen et al (5).…”

Section: Discussionmentioning

confidence: 56%

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Three-dimensional reconstruction of the rat nephron

Christensen

Grann

Kristoffersen

et al. 2014

American Journal of Physiology-Renal Physiology

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This study gives a three-dimensional (3D) structural analysis of rat nephrons and their connections to collecting ducts. Approximately 4,500 2.5-m-thick serial sections from the renal surface to the papillary tip were obtained from each of 3 kidneys of Wistar rats. Digital images were recorded and aligned into three image stacks and traced from image to image. Short-loop nephrons (SLNs), long-loop nephrons (LLNs), and collecting ducts (CDs) were reconstructed in 3D. We identified a well-defined boundary between the outer stripe and the inner stripe of the outer medulla corresponding to the transition of descending thick limbs to descending thin limbs and between the inner stripe and the inner medulla, i.e., the transition of ascending thin limbs into ascending thick limbs of LLNs. In all nephrons, a mosaic pattern of proximal tubule (PT) cells and descending thin limb (DTL) cells was observed at the transition between the PT and the DTL. The course of the LLNs revealed tortuous proximal "straight" tubules and winding of the DTLs within the outer half of the inner stripe. The localization of loop bends of SLNs in the inner stripe of the outer medulla and the bends of LLNs in the inner medulla reflected the localization of their glomeruli; i.e., the deeper the glomerulus, the deeper the bend. Each CD drained approximately three to six nephrons with a different pattern than previously established in mice. This information will provide a basis for evaluation of structural changes within nephrons as a result of physiological or pharmaceutical intervention.rat kidney morphology; three-dimensional structural analysis; digital tracing THE RAT KIDNEY HAS FOR MANY years been the target of a large number of functional and morphological investigations (10 -13, 17) and was recently reviewed (5). In recent years, especially the rat renal medulla has been the subject of intensive comparative structural-functional studies and computer modeling [see e.g., Refs. 15 and 20 and very recently a very comprehensive study on modeling calcium transport in the rat nephron was published (28)]. A prerequisite for conducting these kinds of studies is that the detailed morphology of the kidney is known. However, such a detailed three-dimensional (3D) analysis enabling identification of structural changes at a precisely defined distance from the glomerulus of the different segments along the nephron and collecting duct (CD) in the kidney is currently not available. We have previously described the 3D organization and ultrastructural segmental variation of the mouse kidney nephrons and CDs (29, 32). To describe the variation in kidney morphology in different species, we decided to study the morphology of the rat kidney in detail. We have developed a combined histological and computerized technique, which enables the reconstruction of a large number of rat nephrons in 3D space. Consequently, the present study gives a detailed 3D analysis of rat nephrons, both short-loop nephrons (SLNs) and long-loop nephrons (LLNs), including a description of t...

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Section: Discussionmentioning

confidence: 56%

“…THE RAT KIDNEY HAS FOR MANY years been the target of a large number of functional and morphological investigations (10 -13, 17) and was recently reviewed (5). In recent years, especially the rat renal medulla has been the subject of intensive comparative structural-functional studies and computer modeling [see e.g., Refs.…”

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confidence: 99%

Three-dimensional reconstruction of the rat nephron

Christensen

Grann

Kristoffersen

et al. 2014

American Journal of Physiology-Renal Physiology

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“…15 Although the genetic and cellular bases of cystinosis are clear, little is known on (1) the early structural and molecular changes in the complex kidney architecture leading to the Fanconi syndrome, (2) their significance for cystinosis progression along uriniferous nephron (reviewed in ref. 16 ), (3) the pathogenic role of cystine crystals, and (4) natural adaptation mechanisms. In cystinotic kidneys, Fanconi syndrome is generally attributed to PTC atrophy, starting at the glomerulotubular junction as swanneck deformities, but earlier functional defects caused by impaired gene expression were not considered.…”

mentioning

confidence: 99%

Time Course of Pathogenic and Adaptation Mechanisms in Cystinotic Mouse Kidneys

Chevronnay

Janssens

Smissen

et al. 2014

Journal of the American Society of Nephrology

126

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Cystinosis, a main cause of Fanconi syndrome, is reproduced in congenic C57BL/6 cystinosin knockout (KO) mice. To identify the sequence of pathogenic and adaptation mechanisms of nephropathic cystinosis, we defined the onset of Fanconi syndrome in KO mice between 3 and 6 months of age and analyzed the correlation with structural and functional changes in proximal tubular cells (PTCs), with focus on endocytosis of ultrafiltrated disulfide-rich proteins as a key source of cystine. Despite considerable variation between mice at the same age, typical event sequences were delineated. At the cellular level, amorphous lysosomal inclusions preceded cystine crystals and eventual atrophy without crystals. At the nephron level, lesions started at the glomerulotubular junction and then extended distally. In situ hybridization and immunofluorescence revealed progressive loss of expression of megalin, cubilin, sodiumglucose cotransporter 2, and type IIa sodium-dependent phosphate cotransporter, suggesting apical dedifferentiation accounting for Fanconi syndrome before atrophy. Injection of labeled proteins revealed that defective endocytosis in S1 PTCs led to partial compensatory uptake by S3 PTCs, suggesting displacement of endocytic load and injury by disulfide-rich cargo. Increased PTC apoptosis allowed luminal shedding of cystine crystals and was partially compensated for by tubular proliferation. We conclude that lysosomal storage triggered by soluble cystine accumulation induces apical PTC dedifferentiation, which causes transfer of the harmful load of disulfide-rich proteins to more distal cells, possibly explaining longitudinal progression of swan-neck lesions. Furthermore, our results suggest that subsequent adaptation mechanisms include lysosomal clearance of free and crystalline cystine into urine and ongoing tissue repair.

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“…Our morphological and biochemical data are in concordance with biochemical study which showed strong level of PLAGL1 protein expression in the homogenates of human kidney papilla and medulla with weak expression in the kidney cortex [18]. It has been established that the epithelial cells of any given segment of the uriniferous tubule [divided according to the current morphological nomenclature into the proximal tubule, the intermediate (thin) tubule, the distal tubule and the collecting duct] are homogeneous and distinct for that segment, and that structural differences between them reflect the localization and function of transport proteins and receptors [19]. The different immunoreactivity of the PLAGL1 protein in the various parts of nephron and collecting tubules demonstrated in our study may express its involvement in specific transepithelial transport processes.…”

Section: Pnpla1mentioning

confidence: 99%

PLAGL1 protein is differentially expressed in the nephron segments and collecting ducts in human kidney

Godlewski

Krazinski

Kieżun

et al. 2015

Folia Histochem Cytobiol.

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Introduction. PLAGL1 (pleiomorphic adenoma gene-like 1) is a C2H2-type zinc finger transcription factor associated with the regulation of cell growth and development. Although PLAGL1 expression in kidney was assessed by biochemical methods, the exact localization of the PLAGL1 protein in human kidney has not yet been described. Material and methods. Macroscopically unchanged specimens of kidney tissue were collected from 39 patients undergoing nephrectomy due to renal cell carcinoma. H & E staining of paraffin sections was used to assess histology of the kidney whereas immunohistochemistry was used to localize PLAGL1 protein in kidney compartments. In addition, database sequences search for putative PLAGL1 binding sites among the kidney-related genes was performed. Results. PLAGL1 staining intensity differed depending on the kidney compartment. Strong PLAGL1 immunoreactivity was found in thick ascending limbs of Henle's loop, distal tubules and collecting ducts, whereas PLAGL1 expression in proximal tubules and renal corpuscles (including podocytes) was moderate and weak, respectively. By the in sillico screening of promoter sequences for PLAGL1 specific DNA-binding sites GGG-GCCCC we designated 43 candidate genes for PLAGL1-regulated genes. Analysis of their functional annotations identified three significantly over-represented gene sets: inositol phosphate metabolic processes (GO), endocrine and other factor-regulated calcium reabsorption (KEGG) and calcium signaling pathways (KEGG). Conclusion. Differences in the renal expression of PLAGL1 suggest that this protein may be involved in the regulation of several cellular pathways both as transcriptional factor and coactivator/corepressor of other transcription factors reflecting its role in the cell type-specific control

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Uriniferous Tubule: Structural and Functional Organization

Cited by 56 publications

References 621 publications

Three-dimensional reconstruction of the rat nephron

Three-dimensional reconstruction of the rat nephron

Time Course of Pathogenic and Adaptation Mechanisms in Cystinotic Mouse Kidneys

PLAGL1 protein is differentially expressed in the nephron segments and collecting ducts in human kidney

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