KGFR as a possible therapeutic target in middle ear cholesteatoma.

Abstract

CONCLUSION:

We demonstrated that repression of keratinocyte growth factor (KGF) receptor (KGFR) could be a potentially useful strategy in the conservative treatment of middle ear cholesteatoma.

OBJECTIVES:

Recently, the use of a selective inhibitor of the KGFR, SU5402, in an in vitro experiment resulted in the inhibition of the differentiation and proliferation of epithelial cells through KGF secretion by fibroblasts isolated from the cholesteatoma. In this study, we investigated the effects of the KGFR inhibitor during middle ear cholesteatoma formation in vivo.

METHODS:

Based on the role of KGF in the development of cholesteatoma, Flag-hKGF cDNA driven by CMV14 promoter was transfected through electroporation into the external auditory canal of rats five times on every fourth day. Ears transfected with empty vector were used as controls. KGFR selective inhibitor (SU5402) or MEK inhibitor (PD0325901) was administered in the right ear of five rats after vector transfection. In the control, 2% DMSO in PBS was administered in the other ears after vector transfection.

RESULTS:

The use of a selective KGFR inhibitor, SU5402, completely prevented middle ear cholesteatoma formation in the rats.

• Authors: Tomomi Yamamoto-Fukuda, Naotaro Akiyama, Yasuaki Shibata, Haruo Takahashi, Tohru Ikeda, Michiaki Kohno, Takehiko Koji
• Journal: Acta oto-laryngologica (Acta Otolaryngol) Vol. 134 Issue 11 Pg. 1121-7 (Nov 2014) ISSN: 1651-2251 [Electronic] England
• PMID: 25315911 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Benzamides
• Pyrroles
• SU 5402
• mirdametinib
• Diphenylamine
• Receptor, Fibroblast Growth Factor, Type 2
• keratinocyte growth factor receptor
• Extracellular Signal-Regulated MAP Kinases

Topics

• Animals
• Benzamides
• Cholesteatoma, Middle Ear (metabolism, prevention & control)
• Diphenylamine (analogs & derivatives)
• Drug Evaluation, Preclinical
• Ear Canal (metabolism)
• Extracellular Signal-Regulated MAP Kinases (metabolism)
• Genetic Vectors
• Male
• Pyrroles (therapeutic use)
• Rats, Sprague-Dawley
• Receptor, Fibroblast Growth Factor, Type 2 (antagonists & inhibitors, metabolism)
• Transfection