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Tissue plasminogen activator deficiency promotes early phase regeneration in the olfactory epithelium after bulbectomy

Authors

  • Nobuko Makino MD, PhD,

    Corresponding author
    • Department of Otolaryngology-Head and Neck Surgery, Jichi Medical University School of Medicine, Shimotsuke, Tochigi, Japan
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  • Seiji Madoiwa MD, PhD,

    1. Division of Cell and Molecular Medicine, Center for Molecular Medicine, Jichi Medical University School of Medicine, Shimotsuke, Tochigi, Japan
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  • Tsukasa Ohmori MD, PhD,

    1. Division of Cell and Molecular Medicine, Center for Molecular Medicine, Jichi Medical University School of Medicine, Shimotsuke, Tochigi, Japan
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  • Kazuo Katoh PhD,

    1. Department of Anatomy, Jichi Medical University School of Medicine, Shimotsuke, Tochigi, Japan
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  • Shigeo Ookawara MD, PhD,

    1. Department of Anatomy, Jichi Medical University School of Medicine, Shimotsuke, Tochigi, Japan
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  • Takeharu Kanazawa MD, PhD,

    1. Department of Otolaryngology-Head and Neck Surgery, Jichi Medical University School of Medicine, Shimotsuke, Tochigi, Japan
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  • Osamu Matsuo MD, PhD,

    1. Department of Physiology II, Kinki University School of Medicine, Osaka-sayama City, Japan
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  • Masumi Ichikawa PhD,

    1. Laboratory of Anatomy and Cell Biology, Department of Neuroscience Basic Technology, Tokyo Metropolitan Institute for Neuroscience, Fuchu, Tokyo, Japan
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  • Jun Mimuro MD, PhD,

    1. Division of Cell and Molecular Medicine, Center for Molecular Medicine, Jichi Medical University School of Medicine, Shimotsuke, Tochigi, Japan
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  • Keiichi Ichimura MD, PhD,

    1. Department of Otolaryngology-Head and Neck Surgery, Jichi Medical University School of Medicine, Shimotsuke, Tochigi, Japan
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  • Yoichi Sakata MD, PhD

    1. Division of Cell and Molecular Medicine, Center for Molecular Medicine, Jichi Medical University School of Medicine, Shimotsuke, Tochigi, Japan
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Errata

This article is corrected by:

  1. Errata: Erratum Volume 3, Issue 10, 857, Article first published online: 4 October 2013

  • Potential conflict of interest: None provided.

Correspondence to: Nobuko Makino, MD, PhD, Departments of Otolaryngology–Head and Neck Surgery, Jichi Medical University School of Medicine, 3311–1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan; E-mail: n-makino@jichi.ac.jp

Abstract

Background

Tissue type plasminogen activator (tPA) functions as a fibrinolytic factor in the blood and has unique roles in the nervous system. However, the role of tPA in the olfactory epithelium (OE) is still unclear. Generally, surgical ablation of the olfactory bulb (bulbectomy) triggers degeneration followed by regeneration of OE. In this experimental study, we investigated the role of tPA in OE regeneration.

Methods

Wild-type (WT) mice and tPA-knockout (tPA−/−) mice were subjected to bulbectomy. Reverse-transcription polymerase chain reaction (RT-PCR), in situ hybridization, and immunohistochemical examination was done to detect tPA expression in the olfactory bulb and OE. Cellular proliferation and apoptosis was also monitored in the OE.

Results

Before bulbectomy, tPA was found to be expressed in the olfactory bulb and OE. OE degenerated to a similar extent in both strains between 0 and 3 days after bulbectomy. However, OE was thicker and contained more cells in tPA−/− mice than in WT mice at 7 days after bulbectomy. Moreover, the number of apoptotic bodies was reduced and the number of proliferating cells was increased in the OE of tPA−/− mice compared to WT mice, after bulbectomy. Transmission electron microscopy revealed continuous degeneration of the OE for up to 7 days after bulbectomy in WT mice. In contrast, we observed some intact olfactory vesicles and almost normal supporting cells in the OE of tPA−/− mice, at 7 days after bulbectomy.

Conclusion

The current findings show that the tPA-plasmin system plays an inhibitory role in the regulation of regeneration in the OE.

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