| First Author | Duitman J | Year | 2014 |
| Journal | Lab Invest | Volume | 94 |
| Issue | 1 | Pages | 89-97 |
| PubMed ID | 24247561 | Mgi Jnum | J:206317 |
| Mgi Id | MGI:5550019 | Doi | 10.1038/labinvest.2013.127 |
| Citation | Duitman J, et al. (2014) CCAAT-enhancer binding protein delta (C/EBPdelta) attenuates tubular injury and tubulointerstitial fibrogenesis during chronic obstructive nephropathy. Lab Invest 94(1):89-97 |
| abstractText | CCAAT-enhancer-binding protein delta (C/EBPdelta) 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/EBPdelta would potentiate renal fibrosis. In line with this hypothesis, C/EBPdelta has recently been suggested to regulate the fibrotic response during glomerulonephritis. Here we determined the importance of C/EBPdelta in the development of renal tubulointerstitial fibrosis by subjecting 8- to 12-week-old C/EBPdelta-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/EBPdelta 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-beta. Moreover, we show that the increase in renal fibrosis in C/EBPdelta-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/EBPdelta is a novel mediator of renal fibrosis. Modulating C/EBPdelta expression could consequently be a potential antifibrotic strategy in patients with chronic kidney disease. |
