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Article

Synoviolin inhibitor LS-102 reduces endoplasmic reticulum stress-induced collagen secretion in an in vitro model of stress-related interstitial pneumonia

  • Authors:
    • Fukami Nakajima
    • Satoko Aratani
    • Hidetoshi Fujita
    • Naoko Yagishita
    • Shizuko Ichinose
    • Koshi Makita
    • Yasuhiro Setoguchi
    • Toshihiro Nakajima
  • View Affiliations / Copyright

    Affiliations: Department of Anesthesiology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8519, Japan, Department of Locomotor Science, Institute of Medical Science, Tokyo Medical University, Shinjuku-ku, Tokyo 160-8402, Japan, Institute of Medical Science, St. Marianna University School of Medicine, Kawasaki, Kanagawa 216-8512, Japan, Research Center for Medical and Dental Science, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8510, Japan, Department of Respiratory Medicine, Tokyo Medical University, Shinjuku-ku, Tokyo 160-8402, Japan
  • Pages: 110-116
    |
    Published online on: October 27, 2014
       https://doi.org/10.3892/ijmm.2014.1984
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Abstract

The deletion mutation of exon 4 in surfactant protein C (SP-C), a lung surfactant protein, has been identified in parent-child cases of familial interstitial pneumonia. It has been shown that this mutation induces endoplasmic reticulum (ER) stress. Synoviolin is an E3 ubiquitin ligase that is localized to the ER and is an important factor in the degradation of ER-related proteins. It has been demonstrated that synoviolin is involved in liver fibrosis. In the present study, we investigated the involvement of synoviolin in the pathogenesis of interstitial pneumonia caused by the exon 4 deletion in the SP-C gene. We transfected wild-type and exon 4-deleted SP-C genes into A549 human lung adenocarcinoma cells and measured the secretion of collagen, which is a representative extracellular matrix protein involved in fibrosis. Secreted collagen levels were increased in the culture medium in SP-C mutants compared to the wild-type cells. Furthermore, the transcription of mRNAs coding for factors associated with fibrosis was increased. Subsequently, to assess the involvement of synoviolin, we constructed plasmids with a luciferase gene under the control of the synoviolin promoter. The A549 cells were transfected with the construct along with the exon 4-deleted SP-C plasmid for use in the luciferase assay. We found a 1.6-fold increase in luciferase activaty in the cells carrying exon 4 deleted SP-C, as well as an increase in intrinsic synoviolin expression at the mRNA and protein levels. Collagen secretion was decreased by the addition of LS-102, a synoviolin inhibitor, to the A549 culture medium following transfection with wild-type and exon 4-deleted SP-C. These results demonstrate that synoviolin is involved in the onset of interstitial pneumonia induced by exon 4-deleted SP-C, which suggests that synoviolin inhibitors may be used in the treatment of the disease.
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Copy and paste a formatted citation
Spandidos Publications style
Nakajima F, Aratani S, Fujita H, Yagishita N, Ichinose S, Makita K, Setoguchi Y and Nakajima T: Synoviolin inhibitor LS-102 reduces endoplasmic reticulum stress-induced collagen secretion in an in vitro model of stress-related interstitial pneumonia. Int J Mol Med 35: 110-116, 2015.
APA
Nakajima, F., Aratani, S., Fujita, H., Yagishita, N., Ichinose, S., Makita, K. ... Nakajima, T. (2015). Synoviolin inhibitor LS-102 reduces endoplasmic reticulum stress-induced collagen secretion in an in vitro model of stress-related interstitial pneumonia. International Journal of Molecular Medicine, 35, 110-116. https://doi.org/10.3892/ijmm.2014.1984
MLA
Nakajima, F., Aratani, S., Fujita, H., Yagishita, N., Ichinose, S., Makita, K., Setoguchi, Y., Nakajima, T."Synoviolin inhibitor LS-102 reduces endoplasmic reticulum stress-induced collagen secretion in an in vitro model of stress-related interstitial pneumonia". International Journal of Molecular Medicine 35.1 (2015): 110-116.
Chicago
Nakajima, F., Aratani, S., Fujita, H., Yagishita, N., Ichinose, S., Makita, K., Setoguchi, Y., Nakajima, T."Synoviolin inhibitor LS-102 reduces endoplasmic reticulum stress-induced collagen secretion in an in vitro model of stress-related interstitial pneumonia". International Journal of Molecular Medicine 35, no. 1 (2015): 110-116. https://doi.org/10.3892/ijmm.2014.1984
Copy and paste a formatted citation
x
Spandidos Publications style
Nakajima F, Aratani S, Fujita H, Yagishita N, Ichinose S, Makita K, Setoguchi Y and Nakajima T: Synoviolin inhibitor LS-102 reduces endoplasmic reticulum stress-induced collagen secretion in an in vitro model of stress-related interstitial pneumonia. Int J Mol Med 35: 110-116, 2015.
APA
Nakajima, F., Aratani, S., Fujita, H., Yagishita, N., Ichinose, S., Makita, K. ... Nakajima, T. (2015). Synoviolin inhibitor LS-102 reduces endoplasmic reticulum stress-induced collagen secretion in an in vitro model of stress-related interstitial pneumonia. International Journal of Molecular Medicine, 35, 110-116. https://doi.org/10.3892/ijmm.2014.1984
MLA
Nakajima, F., Aratani, S., Fujita, H., Yagishita, N., Ichinose, S., Makita, K., Setoguchi, Y., Nakajima, T."Synoviolin inhibitor LS-102 reduces endoplasmic reticulum stress-induced collagen secretion in an in vitro model of stress-related interstitial pneumonia". International Journal of Molecular Medicine 35.1 (2015): 110-116.
Chicago
Nakajima, F., Aratani, S., Fujita, H., Yagishita, N., Ichinose, S., Makita, K., Setoguchi, Y., Nakajima, T."Synoviolin inhibitor LS-102 reduces endoplasmic reticulum stress-induced collagen secretion in an in vitro model of stress-related interstitial pneumonia". International Journal of Molecular Medicine 35, no. 1 (2015): 110-116. https://doi.org/10.3892/ijmm.2014.1984
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