Basile, David P.2022-11-182022-11-182022-01Basile, D. P. (2022). Macrophage dynamics in kidney repair: Elucidation of a COX-2–dependent MafB pathway to affect macrophage differentiation. Kidney International, 101(1), 15–18. https://doi.org/10.1016/j.kint.2021.10.02000852538https://hdl.handle.net/1805/30581Following 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 antiinflammatory 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 antiinflammatory drugs that inhibit cyclooxygenase activity.en-USPublisher Policymacrophage polarizationcyclooxygenase 2renal fibrosisArticle