Receptor-mediated endocytosis of α-galactosidase A in human podocytes in Fabry disease

Thaneas Prabakaran; Rikke Nielsen; Jakob Vejby Larsen; Søren S Sørensen; Ulla Feldt-Rasmussen; Moin A Saleem; Claus Munck Petersen; Pierre J Verroust; Erik Ilsø Christensen

doi:10.1371/journal.pone.0025065

Receptor-mediated endocytosis of α-galactosidase A in human podocytes in Fabry disease

Thaneas Prabakaran, Rikke Nielsen, Jakob Vejby Larsen, Søren S Sørensen, Ulla Feldt-Rasmussen, Moin A Saleem, Claus Munck Petersen, Pierre J Verroust, Erik Ilsø Christensen

107 Citationer (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.

Originalsprog	Engelsk
Tidsskrift	P L o S One
Vol/bind	6
Udgave nummer	9
Sider (fra-til)	e25065
ISSN	1932-6203
DOI	https://doi.org/10.1371/journal.pone.0025065
Status	Udgivet - 2011

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10.1371/journal.pone.0025065

Citationsformater

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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 = "Thaneas Prabakaran and Rikke Nielsen and Larsen, {Jakob Vejby} and S{\o}rensen, {S{\o}ren S} and Ulla Feldt-Rasmussen and Saleem, {Moin A} and Petersen, {Claus Munck} and Verroust, {Pierre J} and Christensen, {Erik Ils{\o}}",

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

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TY - JOUR

T1 - Receptor-mediated endocytosis of α-galactosidase A in human podocytes in Fabry disease

AU - Prabakaran, Thaneas

AU - Nielsen, Rikke

AU - Larsen, Jakob Vejby

AU - Sørensen, Søren S

AU - Feldt-Rasmussen, Ulla

AU - Saleem, Moin A

AU - Petersen, Claus Munck

AU - Verroust, Pierre J

AU - Christensen, Erik Ilsø

PY - 2011

Y1 - 2011

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 - Journal article

C2 - 21949853

SN - 1932-6203

VL - 6

SP - e25065

JO - P L o S One

JF - P L o S One

IS - 9

ER -

Receptor-mediated endocytosis of α-galactosidase A in human podocytes in Fabry disease

Abstract

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