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Int. J. Mol. Sci. 2013, 14(7), 14439-14459; doi:10.3390/ijms140714439
Article

Upregulation of Phosphorylated HSP27, PRDX2, GRP75, GRP78 and GRP94 in Acquired Middle Ear Cholesteatoma Growth

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1 Department of Otorhinolaryngology, Kaohsiung Medical University Hospital, Kaohsiung 80756, Taiwan 2 Department of Otorhinolaryngology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80756,Taiwan 3 Department of Food Science and Nutrition, Meiho University, Pingtung 91202, Taiwan 4 Department of Beauty Science, Meiho University, Pingtung 91202, Taiwan 5 Graduate Institute of Applied Health and Biotechnology, Meiho University, Pingtung 91202, Taiwan 6 Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung 80756, Taiwan 7 Department of Pathology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80756, Taiwan 8 Department of Public Health, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80756, Taiwan 9 Department of Preventive Medicine, Kaohsiung Medical University Hospital, Kaohsiung 80756, Taiwan 10 Department of Otorhinolaryngology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung 80756, Taiwan The authors contributed equally to this work.
* Author to whom correspondence should be addressed.
Received: 7 May 2013 / Revised: 26 June 2013 / Accepted: 1 July 2013 / Published: 11 July 2013
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Abstract

Cholesteatoma is a destructive and expanding growth of keratinizing squamous epithelium in the middle ear or petrous apex. The molecular and cellular processes of the pathogenesis of acquired middle ear cholesteatoma have not been fully understood. In this study, comparative proteomic analysis was conducted to investigate the roles of specific proteins in the pathways regarding keratinocyte proliferation in cholesteatoma. The differential proteins were detected by comparing the two-dimension electrophoresis (2-DE) maps of the epithelial tissues of 12 attic cholesteatomas with those of retroauricular skins. There were 14 upregulated proteins in the epithelial tissues of cholesteatoma in comparison with retroauricular skin. The modulation of five crucial proteins, HSP27, PRDX2, GRP75, GRP78 and GRP94, was further determined by RT-PCR, Western blot and immunohistochemistry. Phosphorylation of HSP27 at Ser-82 was identified by mass spectroscopy. The results of this study suggested that phosphorylated HSP27 is the end expression of two potential signal-transduction pathways, and together with PRDX2, they are very likely involved in the proliferation of keratinocytes in cholesteatoma. Upregulations of GRP75, GRP78 and GRP94 in keratinocytes may be able to counter endoplasmic reticulum stress, to inhibit cell apoptosis, to prevent protein unfolding and to promote cholesteatoma growth.
Keywords: cholesteatoma; HSP27; PRDX2; GRP75; GRP78; GRP94 cholesteatoma; HSP27; PRDX2; GRP75; GRP78; GRP94
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Ho, K.Y.; Yeh, T.S.; Huang, H.H.; Hung, K.F.; Chai, C.Y.; Chen, W.T.; Tsai, S.M.; Chang, N.C.; Chien, C.Y.; Wang, H.M.; Wu, Y.J. Upregulation of Phosphorylated HSP27, PRDX2, GRP75, GRP78 and GRP94 in Acquired Middle Ear Cholesteatoma Growth. Int. J. Mol. Sci. 2013, 14, 14439-14459.

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Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert