UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Differential trafficking of albumin and IgG facilitated by the neonatal Fc receptor in podocytes in vitro and in vivo

Dylewski, J; Dobrinskikh, E; Lewis, L; Tonsawan, P; Miyazaki, M; Jat, PS; Blaine, J; (2019) Differential trafficking of albumin and IgG facilitated by the neonatal Fc receptor in podocytes in vitro and in vivo. PLoS One , 14 (2) , Article e0209732. 10.1371/journal.pone.0209732. Green open access

[thumbnail of Dylewsky_journal.pone.0209732.pdf]
Preview
Text
Dylewsky_journal.pone.0209732.pdf - Published Version

Download (2MB) | Preview

Abstract

Proteinuria is strongly associated with kidney disease progression but the mechanisms underlying podocyte handling of serum proteins such as albumin and IgG remain to be elucidated. We have previously shown that albumin and IgG are transcytosed by podocytes in vitro. In other epithelial cells, the neonatal Fc receptor (FcRn) is required to salvage albumin and IgG from the degradative pathway thereby allowing these proteins to be transcytosed or recycled. Here we directly examine the role of FcRn in albumin and IgG trafficking in podocytes by studying handling of these proteins in FcRn knockout (KO) podocytes in vitro and in a podocyte-specific FcRn knockout mice in vivo. In vitro, we find that knockout of FcRn leads to IgG accumulation in podocytes but does not alter albumin trafficking. Similarly, in vivo, podocyte-specific knockout of FcRn does not result in albumin accumulation in podocytes in vivo as measured by mean albumin fluorescence intensity whereas these mice demonstrate significant intraglomerular accumulation of IgG over time. In addition we find that podocyte-specific FcRn KO mice demonstrate mesangial expansion as they age and activation of mesangial cells as demonstrated by increased expression of α-smooth muscle actin. Taken together, these results suggest that trafficking pathways for albumin and IgG differ in podocytes and that sustained disruption of trafficking of plasma proteins alters glomerular structure.

Type: Article
Title: Differential trafficking of albumin and IgG facilitated by the neonatal Fc receptor in podocytes in vitro and in vivo
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pone.0209732
Publisher version: https://doi.org/10.1371/journal.pone.0209732
Language: English
Additional information: Copyright: © 2019 Dylewski et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Keywords: Albumins, Protein transport, Kidneys, Lysosomes, Serum proteins, Mouse models, Urine, Proteinuria
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Institute of Prion Diseases
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Institute of Prion Diseases > MRC Prion Unit at UCL
URI: https://discovery.ucl.ac.uk/id/eprint/10070047
Downloads since deposit
62Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item