Schiessl, Ina Maria and Hammer, Anna and Kattler, Veronika and Gess, Bernhard and Theilig, Franziska and Witzgall, Ralph and Castrop, Hayo (2016) Intravital Imaging Reveals Angiotensin II-Induced Transcytosis of Albumin by Podocytes. JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 27 (3). pp. 731-744. ISSN 1046-6673, 1533-3450
Full text not available from this repository. (Request a copy)Abstract
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 mu m(3) (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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | GLOMERULAR EPITHELIAL-CELLS; ENDOTHELIAL GROWTH-FACTOR; HEYMANN NEPHRITIS; SUBPODOCYTE SPACE; PROXIMAL TUBULE; CAPILLARY WALL; NEPHROTIC RATS; ENDOCYTOSIS; MEGALIN; PROTEINURIA; |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Wolf Hayo Castrop Biology, Preclinical Medicine > Institut für Anatomie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 11 Mar 2019 14:00 |
| Last Modified: | 11 Mar 2019 14:00 |
| URI: | https://pred.uni-regensburg.de/id/eprint/2356 |
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