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Intravital imaging reveals angiotensin II–induced transcytosis of albumin by podocytes

  • Schießl, Ina Maria Institutes of Physiology University of Regensburg, Regensburg, Germany
  • Hammer, Anna Institutes of Physiology University of Regensburg, Regensburg, Germany
  • Kattler, Veronika Institutes of Physiology University of Regensburg, Regensburg, Germany
  • Gess, Bernhard Institutes of Physiology University of Regensburg, Regensburg, Germany
  • Theilig, Franziska Department of Medicine, University of Fribourg, Switzerland
  • Witzgall, Ralph Molecular and Cellular Anatomy, University of Regensburg, Regensburg, Germany
  • Castrop, Hayo Institutes of Physiology University of Regensburg, Regensburg, Germany
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    03.01.2016
Published in:
  • Journal of the American Society of Nephrology. - 2016, vol. 27, no. 3, p. 731–744
English Albuminuria is a hallmark of kidney disease of various etiologies and usually caused by deterioration of glomerular filtration barrier integrity. We recently showed that angiotensin II (Ang II) acutely increases albumin filtration in the healthy kidney. Here, we used intravital microscopy to assess the effects of Ang II on podocyte function in rats. Acute infusion of 30, 60, or 80 ng/kg per minute Ang II enhanced the endocytosis of albumin by activation of the type 1 Ang II receptor and resulted in an average (±SEM) of 3.7±2.2, 72.3±18.6 (P<0.001), and 239.4±34.6 µm³ (P<0.001) albumin-containing vesicles per glomerulus, respectively, compared with none at baseline or 10 ng/kg per minute Ang II. Immunostaining of Ang II–infused kidneys confirmed the presence of albumin-containing vesicles, which colocalized with megalin, in podocin-positive cells. Furthermore, podocyte endocytosis of albumin was markedly reduced in the presence of gentamicin, a competitive inhibitor of megalin-dependent endocytosis. Ang II infusion increased the concentration of albumin in the subpodocyte space, a potential source for endocytic protein uptake, and gentamicin further increased this concentration. Some endocytic vesicles were acidified and colocalized with LysoTracker. Most vesicles migrated from the capillary to the apical aspect of the podocyte and were eventually released into the urinary space. This transcytosis accounted for approximately 10% of total albumin filtration. In summary, the transcellular transport of proteins across the podocyte constitutes a new pathway of glomerular protein filtration. Ang II enhances the endocytosis and transcytosis of plasma albumin by podocytes, which may eventually impair podocyte function.
Faculty
Faculté des sciences et de médecine
Department
Département de Médecine
Language
  • English
Classification
Biology
License
License undefined
Identifiers
Persistent URL
https://folia.unifr.ch/unifr/documents/304857
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