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Myeloid cyclooxygenase-2/prostaglandin E2/E-type prostanoid receptor 4 promotes transcription factor MafB-dependent inflammatory resolution in acute kidney injury
- Source :
- Kidney Int
- Publication Year :
- 2021
-
Abstract
- 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.
- Subjects :
- MafB Transcription Factor
Macrophage polarization
Article
Dinoprostone
chemistry.chemical_compound
Fibrosis
medicine
Humans
Transcription Factor MafB
Kidney
biology
business.industry
Acute kidney injury
Prostanoid
Acute Kidney Injury
medicine.disease
medicine.anatomical_structure
chemistry
Nephrology
MAFB
Cyclooxygenase 2
biology.protein
Cancer research
Prostaglandins
lipids (amino acids, peptides, and proteins)
Cyclooxygenase
business
Receptors, Prostaglandin E, EP4 Subtype
Subjects
Details
- ISSN :
- 15231755
- Volume :
- 101
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Kidney international
- Accession number :
- edsair.doi.dedup.....4e63ed932f789b4f5af9710a75011f56