Cholesteatoma fibroblasts promote epithelial cell proliferation through overexpression of epiregulin.

To investigate whether keratinocytes proliferate in response to epiregulin produced by subepithelial fibroblasts derived from middle ear cholesteatoma. Tissue samples were obtained from patients undergoing tympanoplasty. The quantitative polymerase chain reaction and immunohistochemistry were perfor...

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Autores principales:	Mamoru Yoshikawa, Hiromi Kojima, Yuichiro Yaguchi, Naoko Okada, Hirohisa Saito, Hiroshi Moriyama
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9ef2e9bb6f624116886dad6ba649afbd
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spelling	oai:doaj.org-article:9ef2e9bb6f624116886dad6ba649afbd2021-11-18T07:40:26ZCholesteatoma fibroblasts promote epithelial cell proliferation through overexpression of epiregulin.1932-620310.1371/journal.pone.0066725https://doaj.org/article/9ef2e9bb6f624116886dad6ba649afbd2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23826119/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203To investigate whether keratinocytes proliferate in response to epiregulin produced by subepithelial fibroblasts derived from middle ear cholesteatoma. Tissue samples were obtained from patients undergoing tympanoplasty. The quantitative polymerase chain reaction and immunohistochemistry were performed to examine epiregulin expression and localization in cholesteatoma tissues and retroauricular skin tissues. Fibroblasts were cultured from cholesteatoma tissues and from normal retroauricular skin. These fibroblasts were used as feeder cells for culture with a human keratinocyte cell line (PHK16-0b). To investigate the role of epiregulin in colony formation by PHK16-0b cells, epiregulin mRNA expression was knocked down in fibroblasts by using short interfering RNA and epiregulin protein was blocked with a neutralizing antibody. Epiregulin mRNA expression was significantly elevated in cholesteatoma tissues compared with that in normal retroauricular skin. Staining for epiregulin was more intense in the epithelial cells and subepithelial fibroblasts of cholesteatoma tissues than in retroauricular skin. When PHK16-0b cells were cultured with cholesteatoma fibroblasts, their colony-forming efficiency was 50% higher than when these cells were cultured with normal skin fibroblasts. Also, knockdown of epiregulin mRNA in cholesteatoma fibroblasts led to greater suppression of colony formation than knockdown in skin fibroblasts. Furthermore, the colony-forming efficiency of PHK16-0b cells was significantly reduced after treatment with an epiregulin neutralizing antibody in co-culture with cholesteatoma fibroblasts, but not in co-culture with skin fibroblasts. These results suggest that keratinocyte hyperproliferation in cholesteatoma is promoted through overexpression of epiregulin by subepithelial fibroblasts via epithelial-mesenchymal interactions, which may play a crucial role in the pathogenesis of middle ear cholesteatoma.Mamoru YoshikawaHiromi KojimaYuichiro YaguchiNaoko OkadaHirohisa SaitoHiroshi MoriyamaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 6, p e66725 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Mamoru Yoshikawa Hiromi Kojima Yuichiro Yaguchi Naoko Okada Hirohisa Saito Hiroshi Moriyama Cholesteatoma fibroblasts promote epithelial cell proliferation through overexpression of epiregulin.
description	To investigate whether keratinocytes proliferate in response to epiregulin produced by subepithelial fibroblasts derived from middle ear cholesteatoma. Tissue samples were obtained from patients undergoing tympanoplasty. The quantitative polymerase chain reaction and immunohistochemistry were performed to examine epiregulin expression and localization in cholesteatoma tissues and retroauricular skin tissues. Fibroblasts were cultured from cholesteatoma tissues and from normal retroauricular skin. These fibroblasts were used as feeder cells for culture with a human keratinocyte cell line (PHK16-0b). To investigate the role of epiregulin in colony formation by PHK16-0b cells, epiregulin mRNA expression was knocked down in fibroblasts by using short interfering RNA and epiregulin protein was blocked with a neutralizing antibody. Epiregulin mRNA expression was significantly elevated in cholesteatoma tissues compared with that in normal retroauricular skin. Staining for epiregulin was more intense in the epithelial cells and subepithelial fibroblasts of cholesteatoma tissues than in retroauricular skin. When PHK16-0b cells were cultured with cholesteatoma fibroblasts, their colony-forming efficiency was 50% higher than when these cells were cultured with normal skin fibroblasts. Also, knockdown of epiregulin mRNA in cholesteatoma fibroblasts led to greater suppression of colony formation than knockdown in skin fibroblasts. Furthermore, the colony-forming efficiency of PHK16-0b cells was significantly reduced after treatment with an epiregulin neutralizing antibody in co-culture with cholesteatoma fibroblasts, but not in co-culture with skin fibroblasts. These results suggest that keratinocyte hyperproliferation in cholesteatoma is promoted through overexpression of epiregulin by subepithelial fibroblasts via epithelial-mesenchymal interactions, which may play a crucial role in the pathogenesis of middle ear cholesteatoma.
format	article
author	Mamoru Yoshikawa Hiromi Kojima Yuichiro Yaguchi Naoko Okada Hirohisa Saito Hiroshi Moriyama
author_facet	Mamoru Yoshikawa Hiromi Kojima Yuichiro Yaguchi Naoko Okada Hirohisa Saito Hiroshi Moriyama
author_sort	Mamoru Yoshikawa
title	Cholesteatoma fibroblasts promote epithelial cell proliferation through overexpression of epiregulin.
title_short	Cholesteatoma fibroblasts promote epithelial cell proliferation through overexpression of epiregulin.
title_full	Cholesteatoma fibroblasts promote epithelial cell proliferation through overexpression of epiregulin.
title_fullStr	Cholesteatoma fibroblasts promote epithelial cell proliferation through overexpression of epiregulin.
title_full_unstemmed	Cholesteatoma fibroblasts promote epithelial cell proliferation through overexpression of epiregulin.
title_sort	cholesteatoma fibroblasts promote epithelial cell proliferation through overexpression of epiregulin.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/9ef2e9bb6f624116886dad6ba649afbd
work_keys_str_mv	AT mamoruyoshikawa cholesteatomafibroblastspromoteepithelialcellproliferationthroughoverexpressionofepiregulin AT hiromikojima cholesteatomafibroblastspromoteepithelialcellproliferationthroughoverexpressionofepiregulin AT yuichiroyaguchi cholesteatomafibroblastspromoteepithelialcellproliferationthroughoverexpressionofepiregulin AT naokookada cholesteatomafibroblastspromoteepithelialcellproliferationthroughoverexpressionofepiregulin AT hirohisasaito cholesteatomafibroblastspromoteepithelialcellproliferationthroughoverexpressionofepiregulin AT hiroshimoriyama cholesteatomafibroblastspromoteepithelialcellproliferationthroughoverexpressionofepiregulin
_version_	1718423115596300288

Cholesteatoma fibroblasts promote epithelial cell proliferation through overexpression of epiregulin.

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