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

PloS One
James DylewskiJudith Blaine

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 muscl...Continue Reading

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Citations

Sep 26, 2019·American Journal of Physiology. Cell Physiology·Pantipa TonsawanJudith Blaine
Jun 27, 2020·Archives of Disease in Childhood·Justin PennerHermione Lyall
Dec 8, 2020·American Journal of Physiology. Renal Physiology·Mathieu Lemaire
Apr 4, 2021·International Journal of Molecular Sciences·Toshihiko Tashima
Jan 14, 2022·Immunological Investigations·Aoyang GuoQian Xing

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