Mice lacking CCAAt/enhancer-binding protein-alpha show hyperproliferation of alveolar type II cells and increased surfactant protein mRNAs.
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/EBPalpha-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/EBPalpha-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/EBPalpha-deficient mice than in control mice, which suggests the hyperproliferation of alveolar type II cells in the lungs of the C/EBPalpha-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/EBPalpha-deficient mice. Northern blot analysis revealed that surfactant protein mRNAs were also increased. Thus, these results suggest that C/EBPalpha may play a key role in the proliferation of alveolar type II cells and the regulation of genes of surfactant protein.
Sugahara
K
K
Department of Anesthesiology, University of the Ryukyus Faculty of Medicine, Nishihara, Okinawa, Japan.
Iyama
K I
KI
Kimura
T
T
Sano
K
K
Darlington
G J
GJ
Akiba
T
T
Takiguchi
M
M
D000818:Animals; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000172:deficiency* / Q000235:genetics; D002455:Cell Division; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D018345:Mice, Knockout; D011510:Proteolipids / Q000235:genetics; D011650:Pulmonary Alveoli / Q000378:metabolism* / Q000473:pathology*; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism*
D022763:CCAAT-Enhancer-Binding Protein-alpha; D011510:Proteolipids; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; D012333:RNA, Messenger