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10.1073/pnas.1616457114

http://scihub22266oqcxt.onion/10.1073/pnas.1616457114
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suck abstract from ncbi


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pmid28246329
      Proc+Natl+Acad+Sci+U+S+A 2017 ; 114 (11 ): 2958-2963
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  • Permeation of macromolecules into the renal glomerular basement membrane and capture by the tubules #MMPMID28246329
  • Lawrence MG ; Altenburg MK ; Sanford R ; Willett JD ; Bleasdale B ; Ballou B ; Wilder J ; Li F ; Miner JH ; Berg UB ; Smithies O
  • Proc Natl Acad Sci U S A 2017[Mar]; 114 (11 ): 2958-2963 PMID28246329 show ga
  • 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 ?2 or collagen ?3 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.
  • |Animals [MESH]
  • |Female [MESH]
  • |Glomerular Basement Membrane/*metabolism/ultrastructure [MESH]
  • |Gold [MESH]
  • |Humans [MESH]
  • |Infant [MESH]
  • |Infant, Newborn [MESH]
  • |Kidney Tubules, Proximal/metabolism [MESH]
  • |Kidney Tubules/*metabolism/ultrastructure [MESH]
  • |Macromolecular Substances/*metabolism [MESH]
  • |Male [MESH]
  • |Metal Nanoparticles [MESH]
  • |Mice [MESH]
  • |Microscopy, Confocal [MESH]
  • |Permeability [MESH]


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