| First Author | Hu B | Year | 2012 |
| Journal | Am J Pathol | Volume | 180 |
| Issue | 6 | Pages | 2257-67 |
| PubMed ID | 22503555 | Mgi Jnum | J:184699 |
| Mgi Id | MGI:5426093 | Doi | 10.1016/j.ajpath.2012.02.010 |
| Citation | Hu B, et al. (2012) Mesenchymal-Specific Deletion of C/EBPbeta Suppresses Pulmonary Fibrosis. Am J Pathol 180(6):2257-67 |
| abstractText | The CCAAT/enhancer-binding protein beta (C/EBPbeta) regulates a variety of factors and cellular responses associated with pulmonary fibrosis. To distinguish its role in the mesenchyme from that in other compartments, the effects of mesenchymal-specific deletion of C/EBPbeta on pulmonary fibrosis was examined. Crossing of mice with the floxed C/EBPbeta gene with alpha2(I) collagen enhancer-CreER(T)-bearing mice successfully generated progeny with a conditional knockout (CKO) of C/EBPbeta in collagen I-expressing ("mesenchymal") cells only on treatment with tamoxifen (C/EBPbeta CKO). When treated with an endotracheal bleomycin injection, C/EBPbeta CKO mice showed significant attenuation of pulmonary fibrosis relative to control C/EBPbeta-intact mice. C/EBPbeta CKO mice also had reduced myofibroblasts in the lung. However, no significant differences in inflammatory/immune cell influx were noted in the mutant mice relative to the control mice. DNA microarray and real-time PCR analyses identified a series of myofibroblast differentiation regulators as novel target genes of C/EBPbeta. Interestingly, C/EBPbeta deficiency caused a marked induction of matrix metalloproteinase 12 expression, suggesting its potential role as a repressor, which could account for the noted reduction in fibrosis in the C/EBPbeta-deficient mice. Thus, these findings indicate an essential role for C/EBPbeta in the mesenchymal compartment in pulmonary fibrosis that is independent of its effects on inflammation or immune cell infiltration. |
