Mesenchymal-specific deletion of C/EBPβ suppresses pulmonary fibrosis

16Citations
Citations of this article
29Readers
Mendeley users who have this article in their library.

Abstract

The CCAAT/enhancer-binding protein β (C/EBPβ) 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/EBPβ on pulmonary fibrosis was examined. Crossing of mice with the floxed C/EBPβ gene with α2(I) collagen enhancer-CreER(T)-bearing mice successfully generated progeny with a conditional knockout (CKO) of C/EBPβ in collagen I-expressing ("mesenchymal") cells only on treatment with tamoxifen (C/EBPβ CKO). When treated with an endotracheal bleomycin injection, C/EBPβ CKO mice showed significant attenuation of pulmonary fibrosis relative to control C/EBPβ-intact mice. C/EBPβ 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/EBPβ. Interestingly, C/EBPβ 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/EBPβ-deficient mice. Thus, these findings indicate an essential role for C/EBPβ in the mesenchymal compartment in pulmonary fibrosis that is independent of its effects on inflammation or immune cell infiltration. © 2012 American Society for Investigative Pathology.

Cite

CITATION STYLE

APA

Hu, B., Wu, Z., Nakashima, T., & Phan, S. H. (2012). Mesenchymal-specific deletion of C/EBPβ suppresses pulmonary fibrosis. American Journal of Pathology, 180(6), 2257–2267. https://doi.org/10.1016/j.ajpath.2012.02.010

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free