Intracellular transcytosis of albumin in glomerular endothelial cells after endocytosis through caveolae. Issue 12 (15th May 2017)

• Record Type: Journal Article
• Authors: Moriyama, Takahito; Sasaki, Kayo; Karasawa, Kazunori; Uchida, Keiko; Nitta, Kosaku
• Is Part Of: Journal of cellular physiology. Volume 232:Issue 12(2017:Dec.)
• Page Start: 3565
• Page End: 3573
• Publication Date: 2017-05-15
• Subjects: albumin -- early endosomes -- exocytosis -- glomerular endothelial cells -- transcytosis; Physiology -- Periodicals; Cell physiology -- Periodicals; 571.6
• DOI: 10.1002/jcp.25817
• Languages: English
• ISSNs: 0021-9541

Abstract

Abstract : We previously described albumin endocytosis through caveolae in human renal glomerular endothelial cells (HRGECs). This suggested a new albumin transcytosis pathway, in addition to the fenestral pathway. As a next step, we investigated albumin transcytosis in HRGECs after caveolar endocytosis. HRGECs were incubated with Alexa Fluor 488‐labeled bovine serum albumin from 0 to 360 min. Next, markers for endosomes, endoplasmic reticulum (ER), golgi apparatus (GA), lysosomes, and proteasomes and Fc receptors, microtubules, and actin were monitored by immunofluorescence. Labeled albumin co‐localization with endosomes was gradually and significantly increased and it was significantly higher than with the other markers at any timepoint. Albumin, placed on inside of the Transwell membrane, diffused through HRGEC monolayers during a 360 min incubation period. This transportation of albumin through HRGECs was inhibited by methyl beta cyclodextrin (MBCD), a caveolae disrupting agent. MBCD also decreased albuminuria, causing decreased caveolin‐1 (Cav‐1) expression on glomerular capillaries, in puromycin aminonucleoside induced nephrotic mice. Albumin transcytosis depends on early endosomes, but not on other organelles, Fc receptors, or cytoskeletal components. Caveolae disruption prevented albumin transportation through HRGECs and decreased albuminuria in nephrotic mice. This newly described caveolae‐dependent albumin pathway through glomerular endothelial cells is a potential pathogenetic mechanism for albuminuria, independent of the fenestrae. Abstract : After endocytosis through caveolae into glomerular endothelial cells, albumin was transported to early endosome to sort to bypass lysosomes, proteasomes, the golgi apparatus, and endoplasmic reticulum, and is then transported to the other side of the cells. This newly described caveolae‐dependent albumin pathway through glomerular endothelial cells is a potential pathogenetic mechanism for albuminuria, independent of the fenestrae.