Title |
CCAAT-enhancer binding protein delta (C/EBPδ) attenuates tubular injury and tubulointerstitial fibrogenesis during chronic obstructive nephropathy
|
---|---|
Published in |
Laboratory Investigation, November 2013
|
DOI | 10.1038/labinvest.2013.127 |
Pubmed ID | |
Authors |
JanWillem Duitman, Keren S Borensztajn, Willem P C Pulskens, Jaklien C Leemans, Sandrine Florquin, C Arnold Spek |
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. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Russia | 1 | 7% |
Unknown | 14 | 93% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 4 | 27% |
Student > Master | 2 | 13% |
Professor | 1 | 7% |
Student > Bachelor | 1 | 7% |
Researcher | 1 | 7% |
Other | 1 | 7% |
Unknown | 5 | 33% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 4 | 27% |
Biochemistry, Genetics and Molecular Biology | 3 | 20% |
Medicine and Dentistry | 2 | 13% |
Immunology and Microbiology | 1 | 7% |
Unknown | 5 | 33% |