title: Tissue plasminogen activator deficiency promotes early phase regeneration in the olfactory epithelium after bulbectomy.
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.
  
  
  CONCLUSIONS
  The current findings show that the tPA-plasmin system plays an inhibitory role in the regulation of regeneration in the OE.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Jichi Medical University School of Medicine, Shimotsuke, Tochigi, Japan. n-makino@jichi.ac.jp
authors.forename: Nobuko
authors.initials: N
authors.lastname: Makino
authors.forename: Seiji
authors.initials: S
authors.lastname: Madoiwa
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Ohmori
authors.forename: Kazuo
authors.initials: K
authors.lastname: Katoh
authors.forename: Shigeo
authors.initials: S
authors.lastname: Ookawara
authors.forename: Takeharu
authors.initials: T
authors.lastname: Kanazawa
authors.forename: Osamu
authors.initials: O
authors.lastname: Matsuo
authors.forename: Masumi
authors.initials: M
authors.lastname: Ichikawa
authors.forename: Jun
authors.initials: J
authors.lastname: Mimuro
authors.forename: Keiichi
authors.initials: K
authors.lastname: Ichimura
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Sakata
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D049109:Cell Proliferation; D017403:In Situ Hybridization; D051379:Mice; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D009830:Olfactory Bulb / Q000502:physiology* / Q000601:surgery; D009831:Olfactory Mucosa / Q000378:metabolism / Q000502:physiology*; D012038:Regeneration / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D010959:Tissue Plasminogen Activator / Q000378:metabolism*
chemical_list: D010959:Tissue Plasminogen Activator