Receptor-Mediated Endocytosis of α-Galactosidase A in Human Podocytes in Fabry Disease

T Prabakaran; R Nielsen; JV Larsen; SS Sorensen; UF Rasmussen; MA Saleem; CM Petersen; PJ Verroust; EI Christensen

doi:10.1371/journal.pone.0025065

Receptor-Mediated Endocytosis of α-Galactosidase A in Human Podocytes in Fabry Disease

T Prabakaran, R Nielsen, JV Larsen, SS Sorensen, UF Rasmussen, MA Saleem, CM Petersen, PJ Verroust, EI Christensen

Bristol Medical School (THS)

Research output: Contribution to journal › Article (Academic Journal) › peer-review

104 Citations (Scopus)

Abstract

Injury to the glomerular podocyte is a key mechanism in human glomerular disease and podocyte repair is an important therapeutic target. In Fabry disease, podocyte injury is caused by the intracellular accumulation of globotriaosylceramide. This study identifies in the human podocyte three endocytic receptors, mannose 6-phosphate/insulin-like growth II receptor, megalin, and sortilin and demonstrates their drug delivery capabilities for enzyme replacement therapy. Sortilin, a novel α-galactosidase A binding protein, reveals a predominant intracellular expression but also surface expression in the podocyte. The present study provides the rationale for the renal effect of treatment with α-galactosidase A and identifies potential pathways for future non-carbohydrate based drug delivery to the kidney podocyte and other potential affected organs.

Translated title of the contribution	Receptor-Mediated Endocytosis of α-Galactosidase A in Human Podocytes in Fabry Disease
Original language	English
Pages (from-to)	e25065 - e25065
Number of pages	1
Journal	PLoS ONE
Volume	6(9)
DOIs	https://doi.org/10.1371/journal.pone.0025065
Publication status	Published - Sept 2011

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1371/journal.pone.0025065

Handle.net

Persistent link

Cite this

@article{1389702ec1ae401880195a03be900ae1,

title = "Receptor-Mediated Endocytosis of α-Galactosidase A in Human Podocytes in Fabry Disease",

abstract = "Injury to the glomerular podocyte is a key mechanism in human glomerular disease and podocyte repair is an important therapeutic target. In Fabry disease, podocyte injury is caused by the intracellular accumulation of globotriaosylceramide. This study identifies in the human podocyte three endocytic receptors, mannose 6-phosphate/insulin-like growth II receptor, megalin, and sortilin and demonstrates their drug delivery capabilities for enzyme replacement therapy. Sortilin, a novel α-galactosidase A binding protein, reveals a predominant intracellular expression but also surface expression in the podocyte. The present study provides the rationale for the renal effect of treatment with α-galactosidase A and identifies potential pathways for future non-carbohydrate based drug delivery to the kidney podocyte and other potential affected organs.",

author = "T Prabakaran and R Nielsen and JV Larsen and SS Sorensen and UF Rasmussen and MA Saleem and CM Petersen and PJ Verroust and EI Christensen",

year = "2011",

month = sep,

doi = "10.1371/journal.pone.0025065",

language = "English",

volume = "6(9)",

pages = "e25065 -- e25065",

journal = "PLoS ONE",

issn = "1932-6203",

publisher = "Public Library of Science",

}

TY - JOUR

T1 - Receptor-Mediated Endocytosis of α-Galactosidase A in Human Podocytes in Fabry Disease

AU - Prabakaran, T

AU - Nielsen, R

AU - Larsen, JV

AU - Sorensen, SS

AU - Rasmussen, UF

AU - Saleem, MA

AU - Petersen, CM

AU - Verroust, PJ

AU - Christensen, EI

PY - 2011/9

Y1 - 2011/9

N2 - Injury to the glomerular podocyte is a key mechanism in human glomerular disease and podocyte repair is an important therapeutic target. In Fabry disease, podocyte injury is caused by the intracellular accumulation of globotriaosylceramide. This study identifies in the human podocyte three endocytic receptors, mannose 6-phosphate/insulin-like growth II receptor, megalin, and sortilin and demonstrates their drug delivery capabilities for enzyme replacement therapy. Sortilin, a novel α-galactosidase A binding protein, reveals a predominant intracellular expression but also surface expression in the podocyte. The present study provides the rationale for the renal effect of treatment with α-galactosidase A and identifies potential pathways for future non-carbohydrate based drug delivery to the kidney podocyte and other potential affected organs.

AB - Injury to the glomerular podocyte is a key mechanism in human glomerular disease and podocyte repair is an important therapeutic target. In Fabry disease, podocyte injury is caused by the intracellular accumulation of globotriaosylceramide. This study identifies in the human podocyte three endocytic receptors, mannose 6-phosphate/insulin-like growth II receptor, megalin, and sortilin and demonstrates their drug delivery capabilities for enzyme replacement therapy. Sortilin, a novel α-galactosidase A binding protein, reveals a predominant intracellular expression but also surface expression in the podocyte. The present study provides the rationale for the renal effect of treatment with α-galactosidase A and identifies potential pathways for future non-carbohydrate based drug delivery to the kidney podocyte and other potential affected organs.

U2 - 10.1371/journal.pone.0025065

DO - 10.1371/journal.pone.0025065

M3 - Article (Academic Journal)

C2 - 21949853

SN - 1932-6203

VL - 6(9)

SP - e25065 - e25065

JO - PLoS ONE

JF - PLoS ONE

ER -

Receptor-Mediated Endocytosis of α-Galactosidase A in Human Podocytes in Fabry Disease

Abstract

UN SDGs

Access to Document

Handle.net

Fingerprint

Cite this