ArticleProceedings of the National Academy of Sciences of the United States of America2017
Permeation of macromolecules into the renal glomerular basement membrane and capture by the tubules.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
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70 citing papers in PubMed, 147 citations in OpenAlex.
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- Podocin oligomers regulate the ordering of nephrin chains, providing the molecular basis ofProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Glomerular routing of tumor-derived extracellular vesicles substantiates urinary biopsy.Science advances · 2026Article
- Association of Urinary Complement Peptides with Kidney Function and Progression of Kidney Disease.International journal of molecular sciences · 2026Article
- Molecular Survival Strategies Against Kidney Filtration: Implications for Therapeutic Protein Engineering.Biophysica · 2026Article
- Nanoplastic toxicity and uptake in kidney cells: differential effects of concentration, particle size, and polymer type.Cell biology and toxicology · 2026Article
- The promise of deep urine proteomics for diagnosis of cancer, neurologic, and metabolic diseases.PloS one · 2026Article
- Increased Urinary Albumin Excretion But Less Damaged Renal Tubular Structures in Mice with Genetically DecreasedInnovation discovery · 2026Article
- Evolution-guided design of mini-protein for high-contrastActa pharmaceutica Sinica. B · 2025Article
- pH-Responsive Self-Assembly of Renal-Clearable Nanoparticles in the Kidneys: One Assembly per Endosome.Journal of the American Chemical Society · 2025Article
- Revisiting nephrin signaling and its specialized effects on the uniquely adaptable podocyte.The Biochemical journal · 2025Review
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- Nanoparticle Transport in Proximal Tubules with Rhabdomyolysis-Induced Necrosis.Angewandte Chemie (International ed. in English) · 2025Article
- Exploring the Link Between Renal Function Fluctuations Within the Physiological Range and Serum/CSF Levels of NfL, GFAP, tTAU, and UCHL1.International journal of molecular sciences · 2025Article
- Novel Monoclonal Antibodies 1D2 and 4E4 AgainstJournal of fungi (Basel, Switzerland) · 2024Article
- Localization of albumin with correlative super resolution light- and electron microscopy in the kidney.Journal of structural biology: X · 2024Article
- Discovery of biophysical rate laws from the electronic health record enables real-time liver injury estimation from transaminase dynamics.Cell reports. Medicine · 2024Article
- Linking Basement Membrane and Slit Diaphragm in Drosophila Nephrocytes.Journal of the American Society of Nephrology : JASN · 2024Article
- Allogeneic bone marrow mesenchymal stem cell-derived exosomes alleviate human hypoxic AKI-on-a-Chip within a tight treatment window.Stem cell research & therapy · 2024Article
10 more citing papers are in PubMed but not listed here.
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11 authors at 4 institutions in 2 countries.
Funding
Abstract
How the kidney prevents urinary excretion of plasma proteins continues to be debated. Here, using unfixed whole-mount mouse kidneys, we show that fluorescent-tagged proteins and neutral dextrans permeate into the glomerular basement membrane (GBM), in general agreement with Ogston's 1958 equation describing how permeation into gels is related to molecular size. Electron-microscopic analyses of kidneys fixed seconds to hours after injecting gold-tagged albumin, negatively charged gold nanoparticles, and stable oligoclusters of gold nanoparticles show that permeation into the lamina densa of the GBM is size-sensitive. Nanoparticles comparable in size with IgG dimers do not permeate into it. IgG monomer-sized particles permeate to some extent. Albumin-sized particles permeate extensively into the lamina densa. Particles traversing the lamina densa tend to accumulate upstream of the podocyte glycocalyx that spans the slit, but none are observed upstream of the slit diaphragm. At low concentrations, ovalbumin-sized nanoparticles reach the primary filtrate, are captured by proximal tubule cells, and are endocytosed. At higher concentrations, tubular capture is saturated, and they reach the urine. In mouse models of Pierson's or Alport's proteinuric syndromes resulting from defects in GBM structural proteins (laminin β2 or collagen α3 IV), the GBM is irregularly swollen, the lamina densa is absent, and permeation is increased. Our observations indicate that size-dependent permeation into the lamina densa of the GBM and the podocyte glycocalyx, together with saturable tubular capture, determines which macromolecules reach the urine without the need to invoke direct size selection by the slit diaphragm.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.