TY - JOUR
T1 - Lipid biology of the podocyte-new perspectives offer new opportunities
AU - Fornoni, Alessia
AU - Merscher, Sandra
AU - Kopp, Jeffrey B.
N1 - Funding Information:
A.F. and S.M. are supported by the NIH and NIDDK (grant numbers DK090316 and 5U24DX076169), the National Center for Advancing Translational Sciences (grant number 1UL1TR000460), the Diabetes Research Institute Foundation, the Nephcure Foundation and the Peggy and Harold Katz Family Foundation. S.M. is supported by the Stanley J. Glaser Foundation Research Award. J.B.K. is supported by the NIDDK Intramural Research Program.
PY - 2014/7
Y1 - 2014/7
N2 - 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 A 2 (PLA 2) receptor, which is expressed in podocytes, have been identified. Whether these autoantibodies affect the activity of PLA 2, 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.
AB - 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 A 2 (PLA 2) receptor, which is expressed in podocytes, have been identified. Whether these autoantibodies affect the activity of PLA 2, 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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U2 - 10.1038/nrneph.2014.87
DO - 10.1038/nrneph.2014.87
M3 - Review article
C2 - 24861084
AN - SCOPUS:84903551813
VL - 10
SP - 379
EP - 388
JO - Nature Clinical Practice Nephrology
JF - Nature Clinical Practice Nephrology
SN - 1759-507X
IS - 7
ER -