title: Effects of rapamycin on granulation formation in response to centrally doubled coiled stents as a tracheal substitute.
abstract: BACKGROUND
  In experiments involving tracheal wall defects in rabbits, metallic coil stents inevitably induce granulation formation in the defects. We examined the involvement of the mammalian target of rapamycin (mTOR) signaling pathway in granulation formation and examined the effects of rapamycin.
  
  
  METHODS
  The anterior half of the tracheal wall was removed for a longitudinal length of six tracheal rings. Metallic coils were placed into the tracheal lumen through a wall defect. The rabbits were sacrificed two months after undergoing an endoscopic examination, and the granulation tissue in the tracheal defects was removed for a Western blot analysis and immunohistochemical analysis. Rapamycin (0.5 mg kg(-1) day(-1)) was administered three times per week intramuscularly. The data were expressed as the relative expression versus the expression of actin.
  
  
  RESULTS
  The level of mTOR phosphorylation in the resected trachea was 0.72±0.45, and it significantly increased in the granulation tissue to 11.6±5.2, with concomitant increases in the phosphorylation levels of p70S6K and S6RP in all five rabbits. Although the systemic administration of rapamycin significantly decreased the levels of phosphorylated mTOR to 4.0±2.4 in the five treated rabbits, the clinical outcomes were unsatisfactory. Three of the five treated rabbits exhibited signs of wound complications, and wet granulation tissue that caused respiratory symptoms was found inside and outside of the coils in four rabbits.
  
  
  CONCLUSIONS
  Although rapamycin effectively reduced the mTOR activity in the granulation tissue, the granulation formation process seemed to be disturbed, most likely owing to the immunosuppressive effects of rapamycin.
authors: Department of Pediatric Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan. Electronic address: mkubota@med.niigata-u.ac.jp.
authors: Masayuki
authors: M
authors: Kubota
authors: Yasunobu
authors: Y
authors: Matsuda
authors: Shun
authors: S
authors: Fujimaki
authors: Mami
authors: M
authors: Osawa
authors: Toshifumi
authors: T
authors: Wakai
authors: Kengo
authors: K
authors: Nakaya
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D004334:Drug Administration Schedule; D005549:Foreign-Body Reaction / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D006097:Granulation Tissue / Q000187:drug effects / Q000378:metabolism; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007273:Injections, Intramuscular; D008297:Male; D010766:Phosphorylation / Q000187:drug effects; D011183:Postoperative Complications / Q000378:metabolism / Q000517:prevention & control*; D011817:Rabbits; D020123:Sirolimus / Q000494:pharmacology / Q000627:therapeutic use*; D015607:Stents; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D014132:Trachea / Q000187:drug effects / Q000378:metabolism / Q000601:surgery*; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D007166:Immunosuppressive Agents; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus
keywords: Granulation; Metallic coil; Rapamycin; Tracheal substitute; mTOR