| First Author | Elimam H | Year | 2016 |
| Journal | J Biol Chem | Volume | 291 |
| Issue | 28 | Pages | 14468-82 |
| PubMed ID | 27226532 | Mgi Jnum | J:235458 |
| Mgi Id | MGI:5796429 | Doi | 10.1074/jbc.M115.696781 |
| Citation | Elimam H, et al. (2016) Genetic Ablation of Calcium-independent Phospholipase A2gamma Induces Glomerular Injury in Mice. J Biol Chem 291(28):14468-82 |
| abstractText | 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 A2gamma (iPLA2gamma) is cytoprotective against complement-mediated glomerular epithelial cell injury. Studies in iPLA2gamma KO mice have demonstrated an important role for iPLA2gamma in mitochondrial lipid turnover, membrane structure, and metabolism. The aim of the present study was to employ iPLA2gamma KO mice to better understand the role of iPLA2gamma in normal glomerular and podocyte function as well as in glomerular injury. We show that deletion of iPLA2gamma 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, iPLA2gamma KO mice exhibited significantly increased levels of albuminuria, podocyte injury, and loss of podocytes compared with wild type. Thus, iPLA2gamma has a protective functional role in the normal glomerulus and in glomerulonephritis. Understanding the role of iPLA2gamma in glomerular pathophysiology provides opportunities for the development of novel therapeutic approaches to glomerular injury and proteinuria. |
