| First Author | Elimam H | Year | 2019 |
| Journal | Sci Rep | Volume | 9 |
| Issue | 1 | Pages | 16229 |
| PubMed ID | 31700134 | Mgi Jnum | J:287002 |
| Mgi Id | MGI:6405573 | Doi | 10.1038/s41598-019-52834-x |
| Citation | Elimam H, et al. (2019) Genetic Ablation of Calcium-independent Phospholipase A2gamma Exacerbates Glomerular Injury in Adriamycin Nephrosis in Mice. Sci Rep 9(1):16229 |
| abstractText | Genetic ablation of calcium-independent phospholipase A2gamma (iPLA2gamma) in mice results in marked damage of mitochondria and enhanced autophagy in glomerular visceral epithelial cells (GECs) or podocytes. The present study addresses the role of iPLA2gamma in glomerular injury. In adriamycin nephrosis, deletion of iPLA2gamma exacerbated albuminuria and reduced podocyte number. Glomerular LC3-II increased and p62 decreased in adriamycin-treated iPLA2gamma knockout (KO) mice, compared with treated control, in keeping with increased autophagy in KO. iPLA2gamma KO GECs in culture also demonstrated increased autophagy, compared with control GECs. iPLA2gamma KO GECs showed a reduced oxygen consumption rate and increased phosphorylation of AMP kinase (pAMPK), consistent with mitochondrial dysfunction. Adriamycin further stimulated pAMPK and autophagy. After co-transfection of GECs with mito-YFP (to label mitochondria) and RFP-LC3 (to label autophagosomes), or RFP-LAMP1 (to label lysosomes), there was greater colocalization of mito-YFP with RFP-LC3-II and with RFP-LAMP1 in iPLA2gamma KO GECs, compared with WT, indicating enhanced mitophagy in KO. Adriamycin increased mitophagy in WT cells. Thus, iPLA2gamma has a cytoprotective function in the normal glomerulus and in glomerulopathy, as deletion of iPLA2gamma leads to mitochondrial damage and impaired energy homeostasis, as well as autophagy and mitophagy. |
