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Am J Physiol Renal Physiol 292: F674-F681, 2007. First published October 10, 2006; doi:10.1152/ajprenal.00272.2006 Free Article
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Statin-sensitive endocytosis of albumin by glomerular podocytes

Jeanette Eyre,1 Kyriakos Ioannou,2 Blair D. Grubb,3 Moin A. Saleem,4 Peter W. Mathieson,4 Nigel J. Brunskill,1,3 Erik I. Christensen,5 and Peter S. Topham1,3

1Department of Infection, Immunity, and Inflammation and 3Department of Cell Physiology and Pharmacology, University of Leicester Faculty of Medicine and Biological Sciences, 2Department of Nephrology, Leicester General Hospital, Leicester, and 4Academic and Children's Renal Unit, University of Bristol, Southmead Hospital, Bristol, United Kingdom; and 5Department of Cell Biology, Institute of Anatomy, University of Aarhus, Aarhus, Denmark

Submitted 18 July 2006 ; accepted in final form 5 October 2006

Glomerular podocytes are critical regulators of glomerular permeability via the slit diaphragm and may play a role in cleaning the glomerular filter. Whether podocytes are able to endocytose proteins is uncertain. We studied protein endocytosis in conditionally immortalized mouse and human podocytes using FITC-albumin by direct quantitative assay and by fluorescence microscopy and electron microscopy in mouse podocytes. Furthermore, in vivo uptake was studied in human, rat, and mouse podocytes. Both mouse and human podocytes displayed specific one-site binding for FITC-albumin with Kd of 0.91 or 0.44 mg/ml and Bmax of 3.15 or 0.81 µg/mg cell protein, respectively. In addition, they showed avid endocytosis of FITC-albumin with Km of 9.48 or 4.5 mg/ml and Vmax of 474.3 or 97.4 µg·mg cell protein–1·h–1, respectively. Immunoglobulin and transferrin were inefficient competitors of this process, indicating some specificity for albumin. Accumulation of endocytosed albumin could be demonstrated in intracellular vesicles by fluorescence confocal microscopy and electron microscopy. Endocytosis was sensitive to pretreatment with simvastatin. In vivo accumulation of albumin was found in all three species but was most pronounced in the rat. We conclude that podocytes are able to endocytose protein in a statin-sensitive manner. This function is likely to be highly significant in health and disease. In addition, protein endocytosis by podocytes may represent a useful, measurable phenotypic characteristic against which potentially injurious or beneficial interventions can be assessed.

proteinuria; renal; nephropathy; permeability; slit diaphragm


Address for reprint requests and other correspondence: N. J. Brunskill, Dept. of Nephrology, Leicester General Hospital, Gwendolen Rd., Leicester LE5 4PW, UK (e-mail:njb18{at}le.ac.uk)






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