ArticleJournal of the American Society of Nephrology : JASN2018
Combined Structural and Functional Imaging of the Kidney Reveals Major Axial Differences in Proximal Tubule Endocytosis.
Article in Journal of the American Society of Nephrology : JASN, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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54 citing papers in PubMed.
- Article
- Illuminating Mouse Renal Proximal Tubule Architecture through High-Resolution Volume EM and Machine Learning Analysis.Journal of the American Society of Nephrology : JASN · 2026Article
- Heterogeneity in lysosomal dynamics and metabolic functions along the kidney proximal tubule.Nature communications · 2026Article
- Protein phosphatase 2A subunit B55 alpha is required for angiotensin type 2 receptor elicited natriuresis.American journal of physiology. Renal physiology · 2026Article
- Innovative Technologies for Kidney Research: Three-Dimensional Imaging and Quantification.Seminars in nephrology · 2026Review
- Controlling nephron precursor differentiation to generate proximal-biased kidney organoids with emerging maturity.Nature communications · 2025Article
- Protein handling in kidney tubules.Nature reviews. Nephrology · 2025Review
- Renal nerves and hypertension contribute to impaired proximal tubule megalin-mediated albumin uptake in renovascular hypertensive rats.Hypertension research : official journal of the Japanese Society of Hypertension · 2025Article
- Proximal tubule hypertrophy and hyperfunction: a novel pathophysiological feature in disease states.Clinical kidney journal · 2024Review
- Do Nanoparticles of Calcium Disodium EDTA Minimize the Toxic Effects of Cadmium in Female Rats?Biological trace element research · 2024Article
- The Intricacies of Renal Phosphate Reabsorption-An Overview.International journal of molecular sciences · 2024Review
- Is Chronic Kidney Disease Due to Cadmium Exposure Inevitable and Can It Be Reversed?Biomedicines · 2024Review
- Beyond 2D: A scalable and highly sensitive method for a comprehensive 3D analysis of kidney biopsy tissue.PNAS nexus · 2024Article
- The pathogenesis of albuminuria in cadmium nephropathy.Current research in toxicology · 2024Article
- Navigating the kidney organoid: insights into assessment and enhancement of nephron function.American journal of physiology. Renal physiology · 2023Review
- Evaluation of the efficacy of cystinosin supplementation through CTNS mRNA delivery in experimental models for cystinosis.Scientific reports · 2023Article
- Delivery and Transcriptome Assessment of an In Vitro Three-Dimensional Proximal Tubule Model Established by Human Kidney 2 Cells in Clinical Gelatin Sponges.International journal of molecular sciences · 2023Article
- Dietary supplementation of cystinotic mice by lysine inhibits the megalin pathway and decreases kidney cystine content.Scientific reports · 2023Article
- Receptor-associated protein impairs ligand binding to megalin and megalin-dependent endocytic flux in proximal tubule cells.American journal of physiology. Renal physiology · 2023Article
- A comprehensive mouse kidney atlas enables rare cell population characterization and robust marker discovery.iScience · 2023Article
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11 authors.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundThe kidney proximal convoluted tubule (PCT) reabsorbs filtered macromolecules
methodsTo investigate potential differences in endocytic function in S1 and S2, we quantified ELS protein expression in mouse kidney PCTs using real-time quantitative polymerase chain reaction and immunostaining. We also used multiphoton microscopy to visualize uptake of fluorescently labeled ligands in both living animals and tissue cleared using a modified CLARITY approach.
resultsUptake of proteins by RME occurs almost exclusively in S1. In contrast, dextran uptake by FPE takes place in both S1 and S2, suggesting that RME and FPE are discrete processes. Expression of key ELS proteins, but not megalin, showed a bimodal distribution; levels were far higher in S1, where intracellular distribution was also more polarized. Tissue clearing permitted imaging of ligand uptake at single-organelle resolution in large sections of kidney cortex. Analysis of segmented tubules confirmed that, compared with protein uptake, dextran uptake occurred over a much greater length of the PCT, although individual PCTs show marked heterogeneity in solute uptake length and three-dimensional morphology.
conclusionsStriking axial differences in ligand uptake and ELS function exist along the PCT, independent of megalin expression. These differences have important implications for understanding topographic patterns of kidney diseases and the origins of proteinuria.
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