Mice lacking CCAAT/enhancer-binding protein-? show hyperproliferation of alveolar type II cells and increased surfactant protein mRNAs

Abstract

The lung-specific surfactant proteins (SP) are essential for normal respiratory function. Transcription factors may play an important role in the regulation of surfactant proteins. The CCAAT/enhancer-binding protein (C/EBP) family consists of transcription factors that can stimulate expression of genes in lipid-metabolizing epithelial cells. C/EBPα-deficient mice have been shown to exhibit abnormal pulmonary histopathology. Recently, we demonstrated that C/EBP family members are differentially expressed in alveolar type II cell proliferation and in pulmonary fibrosis. In the present study, to investigate whether the C/EBP family would be involved in the regulation of surfactant proteins, we examined the protein expression of SP-A, and SP-C, and mRNA expression of SP-A, SP-B, and SP-C in the lungs from newborn C/EBPα-deficient mice. Using immunohistochemistry, we demonstrated that positive cells for SP-C, specific to alveolar type II cells, in the lungs were more abundant in the newborn C/EBPα-deficient mice than in control mice, which suggests the hyperproliferation of alveolar type II cells in the lungs of the C/EBPα-deficient mice. In situ hybridization analysis revealed that expression of SP-A, SP-B, and SP-C mRNAs were increased in the lungs of newborn C/EBPα-deficient mice. Northern blot analysis revealed that surfactant protein mRNAs were also increased. Thus, these results suggest that C/EBPα may play a key role in the proliferation of alveolar type II cells and the regulation of genes of surfactant protein.

The polymorphism rs944289 predisposes to papillary thyroid carcinoma through a large intergenic noncoding RNA gene of tumor suppressor type

“…It is known that C/EBPα and C/EBPβ are expressed in thyroid and suppressed in tumor tissue (http://cgap.nci.nih.gov/cgap.html) (30,31). C/EBPα modulates (in collaboration with other transcription factors) expression of tissue-specific genes that results in cell proliferation arrest, tissue development, and differentiation (32)(33)(34)(35)(36). C/EBPα is a major player in hematopoietic differentiation, and its involvement in hematologic malignancies is very well documented (37,38).…”

Airway epithelial cell differentiation during lung organogenesis requires C/EBPα and C/EBPβ

“…In addition, Notch signaling has been suggested to promote differentiation of epithelial precursors toward the Clara cell lineage, at the expense of ciliated cells (Morimoto et al, 2010), and Wnt/b-catenin signaling has been suggested to be important to define the distal airway epithelium and to inhibit differentiation of brochiolar stem cells (Mucenski et al, 2003;Reynolds et al, 2008 (Sugahara et al, 2001). To investigate the consequence of added C/EBPb deletion in C/EBPa-deficient mice, immunodetection of pro-surfactant protein-C (SP-C), a marker for type II pneumocytes (Sugahara et al, 2001), was performed ( Fig. 9A-D).…”

Identification of FGF10 Targets in the Embryonic Lung Epithelium during Bud Morphogenesis

“…Respiratory dysfunction due to inadequate production of lipids and functional surfactant has been described in C/EBP␣ null mice (38,39). C/EBP␣ was excluded from our original list because signals were only marginally detected in one of the samples.…”