Mice lacking CCAAT/enhancer-binding protein-α show hyperproliferation of alveolar type II cells and increased surfactant protein mRNAs (original) (raw)

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.

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Authors and Affiliations

  1. Department of Anesthesiology, University of the Ryukyus Faculty of Medicine, 207 Uehara, Nishihara, Okinawa 903-0215, Japan, , , , ,
    Kazuhiro Sugahara
  2. Department of Surgical Pathology, Kumamoto University School of Medicine, Kumamoto 860-8556, Japan, , , , ,
    Ken-Ichi Iyama
  3. Department of Molecular Genetics, Kumamoto University School of Medicine, Kumamoto 860-8556, Japan, , , , ,
    Tatsuya Kimura
  4. Department of Pediatrics, Kobe University School of Medicine, Kobe 650-0017, Japan, , , , ,
    Kimihiko Sano
  5. Department of Biochemistry, Chiba University School of Medicine, Chiba 260-8670, Japan, , , , ,
    Tsuguno Akiba & Masaki Takiguchi
  6. Department of Pathology and Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA, , , , ,
    Gretchen J. Darlington

Authors

  1. Kazuhiro Sugahara
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  2. Ken-Ichi Iyama
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  3. Tatsuya Kimura
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  4. Kimihiko Sano
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  5. Gretchen J. Darlington
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  6. Tsuguno Akiba
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  7. Masaki Takiguchi
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Sugahara, K., Iyama, KI., Kimura, T. et al. Mice lacking CCAAT/enhancer-binding protein-α show hyperproliferation of alveolar type II cells and increased surfactant protein mRNAs.Cell Tissue Res 306, 57–63 (2001). https://doi.org/10.1007/s004410100420

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