Cholesteatoma fibroblasts promote epithelial cell proliferation through overexpression of epiregulin.
Cholesteatoma fibroblasts promote epithelial cell proliferation through overexpression of epiregulin.
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DOI：
10.1371/journal.pone.0066725
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Moriyama H
中科院分区：
文献类型：
--
作者：
Yoshikawa M;Kojima H;Yaguchi Y;Okada N;Saito H;Moriyama H
研究角质形成细胞是否响应中耳胆脂瘤来源的上皮下成纤维细胞产生的上皮调节蛋白而增殖。 Tissue samples were obtained from patients undergoing tympanoplasty.采用定量聚合酶链反应和免疫组织化学检测胆脂瘤组织和耳后皮肤组织中上皮调节蛋白的表达和定位。 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).为了研究上皮调节蛋白在 PHK16-0b 细胞集落形成中的作用，使用短干扰 RNA 敲低成纤维细胞中上皮调节蛋白 mRNA 的表达，并用中和抗体阻断上皮调节蛋白蛋白。 Epiregulin mRNA expression was significantly elevated in cholesteatoma tissues compared with that in normal retroauricular skin.胆脂瘤组织的上皮细胞和上皮下成纤维细胞中的上皮调节蛋白染色比耳后皮肤中的染色更强烈。当PHK16-0b细胞与胆脂瘤成纤维细胞一起培养时，其集落形成效率比这些细胞与正常皮肤成纤维细胞一起培养时高50%。此外，与皮肤成纤维细胞中的上皮调节蛋白mRNA敲低相比，胆脂瘤成纤维细胞中的上皮调节蛋白mRNA的敲低导致对集落形成的更大抑制。此外，在与胆脂瘤成纤维细胞共培养中，用上皮调节蛋白中和抗体处理后，PHK16-0b细胞的集落形成效率显着降低，但在与皮肤成纤维细胞共培养中则没有。这些结果表明，上皮下成纤维细胞通过上皮间质相互作用过度表达上皮调节蛋白，促进了胆脂瘤中角质形成细胞的过度增殖，这可能在中耳胆脂瘤的发病机制中发挥着至关重要的作用。
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.
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影响因子：
10.3
作者：
El-Ghalbzouri, A;Gibbs, S;Ponec, M
通讯作者：
Ponec, M
影响因子：
11.2
作者：
Hwang, Rosa F.;Moore, Todd;Logsdon, Craig D.
通讯作者：
Logsdon, Craig D.
影响因子：
1.4
作者：
KOJIMA, H;SHIWA, M;MORIYAMA, H
通讯作者：
MORIYAMA, H
影响因子：
11.2
作者：
Koukourakis, MI;Giatromanolaki, A;Sivridis, E
通讯作者：
Sivridis, E
DOI：
10.1073/pnas.0712397105
发表时间：
2008-03-04
影响因子：
11.1
作者：
Li, Shaowei;Takeuchi, Fumiko;Darling, Thomas N.
通讯作者：
Darling, Thomas N.