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: JanWillem Duitman, Keren S Borensztajn, Willem P C Pulskens, Jaklien C Leemans, Sandrine Florquin, C Arnold Spek
• Journal: Laboratory investigation; a journal of technical methods and pathology (Lab Invest) Vol. 94 Issue 1 Pg. 89-97 (Jan 2014) ISSN: 1530-0307 [Electronic] United States
• PMID: 24247561 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CCAAT-Enhancer-Binding Protein-delta

Topics

• Animals
• Apoptosis
• CCAAT-Enhancer-Binding Protein-delta (genetics, metabolism)
• Cell Growth Processes (physiology)
• Female
• Fibrosis (metabolism)
• Immunohistochemistry
• Kidney Tubules (metabolism, pathology)
• Mice
• Mice, Inbred C57BL
• Mice, Transgenic
• Renal Insufficiency, Chronic (metabolism, pathology)
• Statistics, Nonparametric
• Ureteral Obstruction (metabolism, pathology)