title: Genetic Ablation of Calcium-independent Phospholipase A2γ Induces Glomerular Injury in Mice.
abstract: Glomerular visceral epithelial cells (podocytes) play a critical role in the maintenance of glomerular permselectivity. Podocyte injury, manifesting as proteinuria, is the cause of many glomerular diseases. We reported previously that calcium-independent phospholipase A2γ (iPLA2γ) is cytoprotective against complement-mediated glomerular epithelial cell injury. Studies in iPLA2γ KO mice have demonstrated an important role for iPLA2γ in mitochondrial lipid turnover, membrane structure, and metabolism. The aim of the present study was to employ iPLA2γ KO mice to better understand the role of iPLA2γ in normal glomerular and podocyte function as well as in glomerular injury. We show that deletion of iPLA2γ did not cause detectable albuminuria; however, it resulted in mitochondrial structural abnormalities and enhanced autophagy in podocytes as well as loss of podocytes in aging KO mice. Moreover, after induction of anti-glomerular basement membrane nephritis in young mice, iPLA2γ KO mice exhibited significantly increased levels of albuminuria, podocyte injury, and loss of podocytes compared with wild type. Thus, iPLA2γ has a protective functional role in the normal glomerulus and in glomerulonephritis. Understanding the role of iPLA2γ in glomerular pathophysiology provides opportunities for the development of novel therapeutic approaches to glomerular injury and proteinuria.
authors.affiliation: From the Department of Medicine, McGill University Health Centre Research Institute, McGill University, Montreal, Quebec H4A 3J1, Canada and.
authors.forename: Hanan
authors.initials: H
authors.lastname: Elimam
authors.affiliation: From the Department of Medicine, McGill University Health Centre Research Institute, McGill University, Montreal, Quebec H4A 3J1, Canada and.
authors.forename: Joan
authors.initials: J
authors.lastname: Papillon
authors.affiliation: From the Department of Medicine, McGill University Health Centre Research Institute, McGill University, Montreal, Quebec H4A 3J1, Canada and.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Kaufman
authors.affiliation: From the Department of Medicine, McGill University Health Centre Research Institute, McGill University, Montreal, Quebec H4A 3J1, Canada and.
authors.forename: Julie
authors.initials: J
authors.lastname: Guillemette
authors.affiliation: From the Department of Medicine, McGill University Health Centre Research Institute, McGill University, Montreal, Quebec H4A 3J1, Canada and.
authors.forename: Lamine
authors.initials: L
authors.lastname: Aoudjit
authors.affiliation: the Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110.
authors.forename: Richard W
authors.initials: RW
authors.lastname: Gross
authors.affiliation: From the Department of Medicine, McGill University Health Centre Research Institute, McGill University, Montreal, Quebec H4A 3J1, Canada and tomoko.takano@mcgill.ca.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Takano
authors.affiliation: From the Department of Medicine, McGill University Health Centre Research Institute, McGill University, Montreal, Quebec H4A 3J1, Canada and andrey.cybulsky@mcgill.ca.
authors.forename: Andrey V
authors.initials: AV
authors.lastname: Cybulsky
mesh_terms: D000375:Aging; D000818:Animals; D001343:Autophagy; D002478:Cells, Cultured; D059865:Endoplasmic Reticulum Stress; D005921:Glomerulonephritis / Q000235:genetics* / Q000473:pathology; D054522:Group VI Phospholipases A2 / Q000235:genetics*; D007678:Kidney Glomerulus / Q000378:metabolism / Q000473:pathology*; D008565:Membrane Proteins / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008928:Mitochondria / Q000235:genetics / Q000473:pathology; D054512:Phospholipases A2, Calcium-Independent / Q000235:genetics; D050199:Podocytes / Q000378:metabolism / Q000473:pathology*; D011507:Proteinuria / Q000235:genetics / Q000473:pathology
chemical_list: D008565:Membrane Proteins; C113267:nephrin; D054522:Group VI Phospholipases A2; D054512:Phospholipases A2, Calcium-Independent; C516476:Pla2g6 protein, mouse
keywords: Phospholipase A; autophagy; cell injury; glomerulonephritis; mitochondria; podocyte; proteinuria