| First Author | Pan Y | Year | 2022 |
| Journal | Kidney Int | Volume | 101 |
| Issue | 1 | Pages | 79-91 |
| PubMed ID | 34774558 | Mgi Jnum | J:360461 |
| Mgi Id | MGI:7797587 | Doi | 10.1016/j.kint.2021.09.033 |
| Citation | Pan Y, et al. (2022) Myeloid cyclooxygenase-2/prostaglandin E2/E-type prostanoid receptor 4 promotes transcription factor MafB-dependent inflammatory resolution in acute kidney injury. Kidney Int 101(1):79-91 |
| abstractText | Following acute injury to the kidney, macrophages play an important role in recovery of functional and structural integrity, but organ fibrosis and progressive functional decline occur with incomplete recovery. Pro-resolving macrophages are characterized by increased cyclooxygenase 2 (COX-2) expression and this expression was selectively increased in kidney macrophages following injury and myeloid-specific COX-2 deletion inhibited recovery. Deletion of the myeloid prostaglandin E2 (PGE2) receptor, E-type prostanoid receptor 4 (EP4), mimicked effects seen with myeloid COX-2-/- deletion. PGE2-mediated EP4 activation induced expression of the transcription factor MafB in kidney macrophages, which upregulated anti-inflammatory genes and suppressed pro-inflammatory genes. Myeloid Mafb deletion recapitulated the effects seen with either myeloid COX-2 or EP4 deletion following acute kidney injury, with delayed recovery, persistent presence of pro-inflammatory kidney macrophages, and increased kidney fibrosis. Thus, our studies identified a previously unknown mechanism by which prostaglandins modulate macrophage phenotype following acute organ injury and provide new insight into mechanisms underlying detrimental kidney effects of non-steroidal anti-inflammatory drugs that inhibit cyclooxygenase activity. |
