caa a22 4500 606185194 CHVBK 20210128100830.0 cr unu---uuuuu 210128e20151001xx s 000 0 eng 10.1007/s00405-014-3237-6 doi (NATIONALLICENCE)springer-10.1007/s00405-014-3237-6 In vivo over-expression of KGF mimic human middle ear cholesteatoma [Elektronische Daten] [Tomomi Yamamoto-Fukuda, Naotaro Akiyama, Yasuaki Shibata, Haruo Takahashi, Tohru Ikeda, Takehiko Koji] 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 receptorparacrine action play an essential role in middle ear cholesteatoma formation in an in vivo model. Springer-Verlag Berlin Heidelberg, 2014 Middle ear cholesteatoma nationallicence Keratinocyte growth factor (KGF) nationallicence Vivo model nationallicence Electroporation nationallicence Yamamoto-Fukuda Tomomi Department of Histology and Cell Biology, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, 852-8523, Nagasaki, Japan aut Akiyama Naotaro Department of Histology and Cell Biology, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, 852-8523, Nagasaki, Japan aut Shibata Yasuaki Department of Oral Pathology and Bone Metabolism, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan aut Takahashi Haruo Department of Otolaryngology-Head and Neck Surgery, Department of Translational Medical Science, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan aut Ikeda Tohru Department of Oral Pathology and Bone Metabolism, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan aut Koji Takehiko Department of Histology and Cell Biology, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, 852-8523, Nagasaki, Japan aut European Archives of Oto-Rhino-Laryngology Springer Berlin Heidelberg 272/10(2015-10-01), 2689-2696 0937-4477 272:10<2689 2015 272 405 https://doi.org/10.1007/s00405-014-3237-6 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00405-014-3237-6 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Yamamoto-Fukuda Tomomi Department of Histology and Cell Biology, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, 852-8523, Nagasaki, Japan aut NATIONALLICENCE 700 1- Akiyama Naotaro Department of Histology and Cell Biology, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, 852-8523, Nagasaki, Japan aut NATIONALLICENCE 700 1- Shibata Yasuaki Department of Oral Pathology and Bone Metabolism, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan aut NATIONALLICENCE 700 1- Takahashi Haruo Department of Otolaryngology-Head and Neck Surgery, Department of Translational Medical Science, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan aut NATIONALLICENCE 700 1- Ikeda Tohru Department of Oral Pathology and Bone Metabolism, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan aut NATIONALLICENCE 700 1- Koji Takehiko Department of Histology and Cell Biology, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, 852-8523, Nagasaki, Japan aut NATIONALLICENCE 773 0- European Archives of Oto-Rhino-Laryngology Springer Berlin Heidelberg 272/10(2015-10-01), 2689-2696 0937-4477 272:10<2689 2015 272 405