Ultrastructural Features of the Rabbit Proximal Tubules.

Evan, Andrew P.; Gattone, Vincent H.; Connors, Bret A.

doi:10.1679/aohc.55.suppl_139

Cited by 5 publications

(5 citation statements)

References 14 publications

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“…FIGURE 2 presents conventional electron microscopy images comparing rat PTs (note the presence of vacuoles in S1 and S2, organization of mitochondria, and lysosomes; FIGURE 2, A–C ) ( 22 ) and a low ( FIGURE 2 D )- and a high ( FIGURE 2 E )-magnification image with a high-resolution helium ion scanning microscope that shows the impressive expansion of the rat apical PT membrane due to the extensive brush border (BB) but equally as dramatic the extensive lateral ridges that increase the basolateral membrane (BLM) surface area ( 23 ). An earlier study looking at rabbit PTs with scanning electron microscopy (SEM) had also documented this incredible expansion of both apical and basolateral membranes while also highlighting the numerous smaller microvilli located at the base of the lateral ridges (LRs) in contact with the basement membrane (BM) ( 12 ). Note that we still do not completely understand how these structural adaptations are utilized by the PTs to perform their varied and important transport functions ( 13 ).…”

Section: Proximal Tubulementioning

confidence: 99%

Albumin uptake and processing by the proximal tubule: physiological, pathological, and therapeutic implications

Molitoris

Sandoval

Yadav

et al. 2022

Physiological Reviews

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For nearly fifty years the proximal tubule has been known to reabsorb, process, and either catabolize or transcytose albumin from the glomerular filtrate. Innovative techniques and approaches have provided insights into these processes, and several genetic diseases, nonselective proximal tubule cell (PTC) defects, chronic kidney disease and acute PTC injury lead to significant albuminuria, reaching nephrotic range. Albumin is also known to stimulate PTC injury cascades. Thus, the mechanisms of albumin reabsorption, catabolism and transcytosis are being reexamined utilizing techniques that allow for novel molecular and cellular discoveries. Megalin, a scavenger receptor, cubilin, amnionless, and Dab2 form a nonselective multi-receptor complex that mediates albumin binding, uptake and directs proteins for lysosomal degradation following endocytosis. The neonatal Fc receptor mediates albumin transcytosis by its pH-dependent binding affinity in endosomal compartments. This transcytotic, reclamation, pathway minimizes urinary losses and cellular catabolism of albumin thus prolonging its serum half-life. It also serves as a PTC molecular sorting mechanism to preserve and reclaim physiologic albumin while allowing "altered" albumin that does not bind to FcRn to enter the lysosomal pathway. The clinical importance of PTC albumin metabolism has also increased as albumin is now being used to bind therapeutic agents to extend their half-life and minimize filtration and kidney injury. The purpose of this review is to update and integrate evolving information regarding the reabsorption and processing of albumin by proximal tubule cells including discussing genetic disorders and therapeutic considerations.

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Section: Proximal Tubulementioning

confidence: 99%

Albumin uptake and processing by the proximal tubule: physiological, pathological, and therapeutic implications

Molitoris

Sandoval

Yadav

et al. 2022

Physiological Reviews

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“…The segments in the tubule vary in their roles in this process, differentially reabsorbing water and solutes [25,26]. More distal segments of the tubule fine-tune the excretion of water, urea, calcium, potassium, and other solutes through reclamation or secretory processes.…”

Section: Formation Of Urinementioning

confidence: 99%

Sources of urinary proteins and their analysis by urinary proteomics for the detection of biomarkers of disease

Julian

Suzuki

et al. 2009

Proteomics Clinical Apps

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Renal disorders account for a substantial fraction of the budget for health care in many countries. Proteinuria is a frequent manifestation in afflicted patients, but the origin of the proteins varies based on the nature of the disorder. The emerging field of urinary proteomics has the potential to replace kidney biopsy as the diagnostic procedure of choice for patients with some glomerular forms of renal disease. To fully realize this potential, it is vital to understand the basis for the urinary excretion of protein in physiological and pathological conditions. In this review, we discuss the structure of the nephron, the functional unit of the kidney, and the process by which proteins/peptides enter the urine. We discuss several aspects of proteinuria that impact the proteomic analysis of urine of patients with renal diseases. KeywordsGlomerular Filtration; Nephron; Proteinuria; Proteomics; Renal Tubule Twenty-four hundred years ago, Hippocrates noted the association between bubbles on the surface of voided urine and kidney disease. This foamy appearance is due to proteinuria, an abnormality oftentimes discovered during routine evaluations in the primary-care setting. The clinical significance of this finding varies widely. Some individuals will be shown to have a benign cause, such as fever, intense activity, exercise, orthostatic proteinuria, or acute illness. Alternatively, serious conditions include a host of ailments intrinsic to the kidney (glomerulonephritis, tubular disorders, interstitial renal disease, and hypertensive renal damage) and various extra-renal disorders (plasma cell dyscrasia, inflammation of the urinary tract, and uroepithelial tumors). To ensure an accurate and timely diagnosis, a knowledgeable approach to the evaluation of proteinuria is critical. Structure of the nephronThe functional unit of the kidney is the nephron and each normal human kidney contains about 1 × 10 6 such units. Its essential components are the glomerulus and the tubule (Figure 1). The glomerulus is the site of formation of the primary urine. It is composed of a capillary network Corresponding Author: Bruce A. Julian, M.D., Division of Nephrology THT 643, 1530 Third Avenue South, Birmingham, AL 35294, USA, Tel: 1-205-934-9045, Fax: 1-205-934-7742, bjulian@uab.edu. Conflict of interest statementThe authors do not have any financial/commercial conflicts of interest to declare. NIH Public Access Author ManuscriptProteomics Clin Appl. Author manuscript; available in PMC 2010 August 26. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscriptlined by a thin layer of endothelial cells separated from overlying epithelial cells (podocytes) by a basement membrane. Bowman's space is covered by epithelial cells and is the collection site for the primary urine. Upon exiting this space, the urine enters the tubule where its composition is drastically altered before leaving the kidney. The tubule can be divided into several functional segments that differ in their capacities to reabsorb solutes, prote...

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“…What might be the functional importance of such feto‐fetal membrane appositions? Microvilli of the brush‐border in the mammalian gut and the membranes basal invaginations in renal tubules show a similar apposition of two membranes of one cell, separated from each other by an intercellular space (Evan, Gattone, & Connors, ; Walton, Freddo, Wang, & Gumucio, ). In both cases these membrane arrangements facilitate intensive substance transport.…”

Section: Discussionmentioning

confidence: 99%

Evolutionary implications of fetal and maternal microvillous surfaces in epitheliochorial placentae

Kazemian

Hooshmandabbasi

Schraner

et al. 2019

Journal of Morphology

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According to the “parent‐offspring conflict hypothesis” the rapid evolution and diversification of the mammalian placenta is driven by divergent optima of resource allocation between fetus and mother. The fetus has an interest to maximize its resource intake, while the mother has an interest to restrict the transfer of resources, and thus retain resources for subsequent pregnancies. In the epitheliochorial placenta, the contacting fetal and maternal surfaces at the feto‐maternal interface are covered with microvilli, which leads to an increase of membrane surfaces available for transport processes. Because membranes are the site of active transport, the conflict hypothesis predicts that the fetal surfaces at the feto‐maternal interfaces are larger than the maternal ones. We use transmission electron microscopy and a stereological method to estimate the factors by which the apical fetal and maternal membranes are enlarged by the microvilli. Ten species with an epitheliochorial placenta were studied. Focused ion beam—scanning electron microscopy (FIB‐SEM) was used to create three‐dimensional models of the interdigitating microvilli of the bovine and porcine placenta. In all species, the fetal surface was larger than the maternal. This was due to a higher number of fetal microvilli and to the presence of membrane folds at the base of the fetal, but not of maternal microvilli. Our results suggest that the ultrastructural morphology of the feto‐maternal interface in the epitheliochorial placenta is shaped by conflicting interests between fetus and mother and thus represent a so far neglected arena of the parent‐offspring conflict.

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Ultrastructural Features of the Rabbit Proximal Tubules.

Cited by 5 publications

References 14 publications

Albumin uptake and processing by the proximal tubule: physiological, pathological, and therapeutic implications

Albumin uptake and processing by the proximal tubule: physiological, pathological, and therapeutic implications

Sources of urinary proteins and their analysis by urinary proteomics for the detection of biomarkers of disease

Evolutionary implications of fetal and maternal microvillous surfaces in epitheliochorial placentae

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