| First Author | Montford JR | Year | 2018 |
| Journal | J Lipid Res | Volume | 59 |
| Issue | 2 | Pages | 380-390 |
| PubMed ID | 29229740 | Mgi Jnum | J:257474 |
| Mgi Id | MGI:6115079 | Doi | 10.1194/jlr.M082362 |
| Citation | Montford JR, et al. (2018) Bone marrow-derived cPLA2alpha contributes to renal fibrosis progression. J Lipid Res 59(2):380-390 |
| abstractText | The group IVA calcium-dependent cytosolic phospholipase A2 (cPLA2alpha) enzyme directs a complex "eicosanoid storm" that accompanies the tissue response to injury. cPLA2alpha and its downstream eicosanoid mediators are also implicated in the pathogenesis of fibrosis in many organs, including the kidney. We aimed to determine the role of cPLA2alpha in bone marrow-derived cells in a murine model of renal fibrosis, unilateral ureteral obstruction (UUO). WT C57BL/6J mice were irradiated and engrafted with donor bone marrow from either WT mice [WT-bone marrow transplant (BMT)] or mice deficient in cPLA2alpha (KO-BMT). After full engraftment, mice underwent UUO and kidneys were collected 3, 7, and 14 days after injury. Using picrosirius red, collagen-3, and smooth muscle alpha actin staining, we determined that renal fibrosis was significantly attenuated in KO-BMT animals as compared with WT-BMT animals. Lipidomic analysis of homogenized kidneys demonstrated a time-dependent upregulation of pro-inflammatory eicosanoids after UUO; KO-BMT animals had lower levels of many of these eicosanoids. KO-BMT animals also had fewer infiltrating pro-inflammatory CD45+CD11b+Ly6C(hi) macrophages and reduced message levels of pro-inflammatory cytokines. Our results indicate that cPLA2alpha and/or its downstream mediators, produced by bone marrow-derived cells, play a major role in eicosanoid production after renal injury and in renal fibrinogenesis. |
