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Intravital Imaging Reveals Angiotensin II‐induced Endocytosis and Shedding of Plasma Albumin by Podocytes
Author(s) -
Schießl Ina,
Kattler Veronika,
Hammer Anna,
Castrop Hayo
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.970.3
Subject(s) - podocyte , angiotensin ii , endocytosis , losartan , endocytic cycle , chemistry , albumin , nephrin , medicine , endocrinology , podocin , kidney , receptor , biology , biochemistry , proteinuria
We recently showed that angiotensin II (ANGII) acutely increases the albumin filtration in the healthy kidney. Here we used intravital microscopy to assess the effects of ANGII on podocyte function in rats. Acute infusion of 0, 10, 30, 60, and 80 ng/kg/min ANGII enhanced the endocytosis of albumin and resulted in an average of 0, 0, 3.7±2.2, 72.3±18.6 (p=0.0004) and 239.4±34.6 µm 3 (p<0.0001), respectively, of albumin‐containing vesicles/glomerulus. This effect was abolished in the presence of the AT1 receptor antagonist losartan. Immunostainings of ANGII‐infused kidneys confirmed the presence of albumin‐containing vesicles in the podocytes, which colocalized with podocin and the multiligand receptor megalin. Furthermore, in the presence of gentamicin, podocyte endocytosis of albumin was markedly reduced to 1.5±1.5 and 22.5±6.3 µm 3 during infusion of 60 and 80 ng/kg/min ANGII (p=.0025 and .0001 vs. non‐gentamicin‐treated rats, respectively), suggesting a megalin‐dependent uptake mechanism. ANGII infusion increased the concentration of albumin in the subpodocyte space, a potential source for endocytic protein uptake, and this concentration was further increased in the presence of gentamicin. Some of the endocytic vesicles were acidified, and colocalized with the lysosomal marker lysotracker in vivo , suggesting lysosomal degradation. Another subset of vesicles migrated from the capillary to the apical aspect of the podocyte and was eventually shed into the urinary space. In summary, the transcellular transport of proteins across the podocyte constitutes a new pathway of glomerular protein filtration. ANGII enhances the endocytosis and shedding of plasma albumin by podocytes and this may eventually impair podocyte function.