title: CCAAT-enhancer binding protein delta (C/EBPδ) attenuates tubular injury and tubulointerstitial fibrogenesis during chronic obstructive nephropathy.
abstract: CCAAT-enhancer-binding protein delta (C/EBPδ) is a transcription factor mainly known for its role in inflammation and apoptosis/proliferation. Considering that these are key processes in renal fibrosis, we hypothesized that C/EBPδ would potentiate renal fibrosis. In line with this hypothesis, C/EBPδ has recently been suggested to regulate the fibrotic response during glomerulonephritis. Here we determined the importance of C/EBPδ in the development of renal tubulointerstitial fibrosis by subjecting 8- to 12-week-old C/EBPδ-deficient mice and age- and sex-matched wild-type controls to the unilateral ureteral obstruction model. Mice were killed at 1, 3, or 7 days post surgery, and renal tissues were obtained for RNA, protein, and immunohistochemical analysis. We show that C/EBPδ deficiency resulted in a more profound fibrotic response as evident from enhanced tubular injury, collagen deposition in the interstitial area, and higher expression of transforming growth factor-β. Moreover, we show that the increase in renal fibrosis in C/EBPδ-deficient mice does not depend on an altered proliferation/apoptosis balance or on a differential inflammatory response in the obstructed kidney. In conclusion, our study provides direct evidence that C/EBPδ is a novel mediator of renal fibrosis. Modulating C/EBPδ expression could consequently be a potential antifibrotic strategy in patients with chronic kidney disease.
authors.affiliation: Center for Experimental and Molecular Medicine (CEMM), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: JanWillem
authors.initials: J
authors.lastname: Duitman
authors.affiliation: Unité INSERM 700, Physiopathologie et Epidémiologie de l'Insuffisance Respiratoire, Faculté de Médecine Xavier Bichat, Paris, France.
authors.forename: Keren S
authors.initials: KS
authors.lastname: Borensztajn
authors.affiliation: Department of Physiology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: Willem P C
authors.initials: WP
authors.lastname: Pulskens
authors.affiliation: Department of Pathology; Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Jaklien C
authors.initials: JC
authors.lastname: Leemans
authors.affiliation: 1] Department of Pathology; Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands [2] Department of Pathology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Florquin
authors.affiliation: Center for Experimental and Molecular Medicine (CEMM), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: C Arnold
authors.initials: CA
authors.lastname: Spek
mesh_terms: D000818:Animals; D017209:Apoptosis; D051743:CCAAT-Enhancer-Binding Protein-delta / Q000235:genetics / Q000378:metabolism*; D048708:Cell Growth Processes / Q000502:physiology; D005260:Female; D005355:Fibrosis / Q000378:metabolism; D007150:Immunohistochemistry; D007684:Kidney Tubules / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D051436:Renal Insufficiency, Chronic / Q000378:metabolism* / Q000473:pathology*; D018709:Statistics, Nonparametric; D014517:Ureteral Obstruction / Q000378:metabolism / Q000473:pathology
chemical_list: D051743:CCAAT-Enhancer-Binding Protein-delta