In vivo over-expression of KGF mimic human middle ear cholesteatoma

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• 作者：Tomomi Yamamoto-Fukuda ; Naotaro Akiyama…
• 关键词：Middle ear cholesteatoma ; Keratinocyte growth factor (KGF) ; Vivo model ; Electroporation
• 刊名：European Archives of Oto-Rhino-Laryngology
• 出版年：2015
• 出版时间：October 2015
• 年：2015
• 卷：272
• 期：10
• 页码：2689-2696
• 全文大小：2,111 KB
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• 作者单位：Tomomi Yamamoto-Fukuda (1) (2)
  Naotaro Akiyama (1) (2)
  Yasuaki Shibata (3)
  Haruo Takahashi (2)
  Tohru Ikeda (3)
  Takehiko Koji (1)
  
  1. Department of Histology and Cell Biology, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki, 852-8523, Japan
  2. Department of Otolaryngology-Head and Neck Surgery, Department of Translational Medical Science, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
  3. Department of Oral Pathology and Bone Metabolism, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
  
• 刊物类别：Medicine
• 刊物主题：Medicine & Public Health
  Otorhinolaryngology
  Neurosurgery
  Head and Neck Surgery
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：1434-4726

文摘

We reported previously that keratinocyte growth factor (KGF), a mesenchymal cell-derived paracrine growth factor, plays an important role in middle ear cholesteatoma formation, which is characterized by marked proliferation of epithelial cells. Here, we investigated whether KGF, the main factor that induces cholesteatoma, overexpression in vivo results in the formation of cholesteatoma. Flag-hKGF cDNA driven by CMV14 promoter was transfected through electroporation into the external auditory canal (EAC) of rats once (short-term model) or five times on every fourth day (long-term model). Ears transfected with empty vector were used as controls. Successful transfection of plasmids into epithelial and stromal cells was confirmed by Flag immunohistochemistry. In the short-term model, the intensity of KGF protein was the strongest in hKGF transfected ear at day 4. KGF expression induced epithelial cell proliferation, reaching a peak level at day 4 and then decreased later, while in the long-term model, KGF expression in the EAC led to middle ear cholesteatoma formation. In conclusion, we described here a new experimental model of human middle ear cholesteatoma, and demonstrated that KGF and KGF receptor paracrine action play an essential role in middle ear cholesteatoma formation in an in vivo model. Keywords Middle ear cholesteatoma Keratinocyte growth factor (KGF) Vivo model Electroporation