Renal Tubule Albumin Transport

Abstract

Albumin is the most abundant protein in serum and contributes to the maintenance of oncotic pressure as well as to transport of hydrophobic molecules. Although albumin is a large anionic protein, it is not completely retained by the glomerular filtration barrier. In order to prevent proteinuria, albumin is reabsorbed along the proximal tubules by receptor-mediated endocytosis, which involves the binding proteins megalin and cubilin. Endocytosis depends on proper vesicle acidification. Disturbance of endosomal acidification or loss of the binding proteins leads to tubular proteinuria. Furthermore, endocytosis is subject to modulation by different signaling systems, such as protein kinase A (PKA), protein kinase C (PKC), phosphatidylinositol 3-kinase (PI3-K) and transforming growth factor beta (TGF-beta). In addition to being reabsorbed in the proximal tubule, albumin can also act as a profibrotic and proinflammatory stimulus, thereby initiating or promoting tubulo-interstitial diseases.

Albumin endocytosis in proximal tubule cells is modulated by angiotensin II through an AT 2 receptor-mediated protein kinase B activation

“…These data indicate that the mechanisms of signal transduction involved in AT 2 -mediated activation of PKB observed in our studies are very different from those reported for AT 1 -medited activation (18,19).…”

“…To investigate which Ang II receptor is involved in the modulation of the albumin endocytosis, LLC-PK1 cells were treated with losartan and PD123319, specific antagonists for AT 1 and AT 2 receptors, respectively (Fig. 2).…”

“…I n the normal human adult, Ϸ7 g of albumin daily is filtered by the glomerulus, most of it effectively reabsorbed in the proximal tubule (1). Albuminuria caused by increased glomerular filtration or tubular injury is a well known marker for renal disease with direct evidence for its involvement in the progression of chronic kidney disease to end-stage renal failure (2).…”

“…Albumin reabsorption by proximal tubule cells occurs by clathrin-and receptor-mediated endocytosis, where the binding of albumin involves at least the complex of two proteins, megalin and cubilin (1). Under normal circumstances, endocytosis prevents the loss of albumin in urine.…”

Two cases of minor glomerular abnormalities with proteinuria disproportionate to the degree of hypoproteinemia

“…b, c Hyaline droplet degeneration (black arrows) in the proximal convoluted tubule epithelium (b hematoxylin-eosin stain 9400, c periodic acid-methenamine silver stain 9400). d Electron microscopy showed more than 80 % foot process effacement (white arrows) with no electron-dense deposits As mentioned above, proteins that leak through the glomerulus combine with megalin and cubilin in the PTE and are taken into cells via endocytosis and reabsorbed in the blood after being disintegrated into amino acids in endosomes by lysosomal enzymes [8]. In addition, the possibility that the albumin taken into cells is collected via transcytosis has been reported.…”