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Nat Rev Nephrol. 2014 Jul;10(7):379-88. doi: 10.1038/nrneph.2014.87. Epub 2014 May 27.

Lipid biology of the podocyte--new perspectives offer new opportunities.

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Peggy and Harold Katz Family Drug Discovery Center, Division of Nephrology and Hypertension, University of Miami Miller School of Medicine, 1580 North West 10th Avenue, Miami, FL 33136, USA.
Kidney Disease Section, Kidney Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, 10 Center Drive, 3N116 Bethesda, MD 20892-1268, USA.


In the past 15 years, major advances have been made in understanding the role of lipids in podocyte biology. First, susceptibility to focal segmental glomerulosclerosis (FSGS) and glomerular disease is associated with an APOL1 sequence variant, is expressed in podocytes and encodes apolipoprotein L1, an important component of HDL. Second, acid sphingomyelinase-like phosphodiesterase 3b encoded by SMPDL3b has a role in the conversion of sphingomyelin to ceramide and its levels are reduced in renal biopsy samples from patients with recurrent FSGS. Furthermore, decreased SMPDL3b expression is associated with increased susceptibility of podocytes to injury after exposure to sera from these patients. Third, in many individuals with membranous nephropathy, autoantibodies against the phospholipase A2 (PLA2) receptor, which is expressed in podocytes, have been identified. Whether these autoantibodies affect the activity of PLA2, which liberates arachidonic acid from glycerophospholipids and modulates podocyte function, is unknown. Fourth, clinical and experimental evidence support a role for ATP-binding cassette sub-family A member 1-dependent cholesterol efflux, free fatty acids and glycerophospolipids in the pathogenesis of diabetic kidney disease. An improved understanding of lipid biology in podocytes might provide insights to develop therapeutic targets for primary and secondary glomerulopathies.

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