首页> 外文期刊>JAMA otolaryngology-- head & neck surgery >Regulation of the Angiogenesis of Acquired Middle Ear Cholesteatomas by Inhibitor of DNA Binding Transcription Factor
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Regulation of the Angiogenesis of Acquired Middle Ear Cholesteatomas by Inhibitor of DNA Binding Transcription Factor

机译:DNA结合转录因子抑制剂对获得性中耳胆脂瘤的血管生成的调节。

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Importance: The aggressive growth of cholesteatoma in the middle ear involves the angiogenesis of the cho-lesteatomal perimatrix. However, which transcription factor is involved in this process remains unclear. Objective: To identify a transcription factor that supports the aggressive growth of cholesteatoma by controlling the angiogenesis of cholesteatoma in the middle ear milieu. Design: We used clinical specimens for the profiling of angiogenic factors and their regulatory transcription factors in cholesteatoma. Human skin keratinocytes and en-dothelial cells were used for evaluation of the effects of candidate transcription factor on the angiogenic factor regulation and endothelial cell proliferation. Setting: University departments of otolaryngology-head and neck surgery. Participants: Eight clinical cholesteatomal and 8 control specimens were used for cellular and molecular biologic evaluation. An additional 8 cholesteatomal and 8 aural skin specimens were used for microarray studies. Main Outcome Measures: The expression of vascular endothelial growth factor, interleukin 8, and cyclooxy-genase 2 as measured by means of immunohis to chemistry and molecular biologic methods. Results: Human aural cholesteatomal specimens were rich in the expression of angiogenic factors such as vascular endothelial growth factor in the cholesteatomal matrix and perimatrix, accompanied by the transcription factor inhibitor of DNA binding (Id1). We found Id1 to be an essential regulator of vascular endothelial growth factor. In addition, potent angiogenic factors, including interleukin 8 and cyclooxygenase 2, were regulated by Idl via different molecular mechanisms. Conclusions and Relevance: The transcription factor Idl controls the angiogenesis of cholesteatoma through the regulation of vascular endothelial growth factor, interleukin 8, and cyclooxygenase 2, which are responsible for the angiogenesis of cholesteatoma. Idl may serve as a good target for the treatment of cholesteatomal progression in the middle ear milieu.
机译:重要性:胆脂瘤在中耳的侵袭性生长涉及胆总管周围皮层的血管生成。但是,尚不清楚该过程涉及哪个转录因子。目的:通过控制中耳环境中胆脂瘤的血管生成,确定支持胆脂瘤生长的转录因子。设计:我们使用临床标本对胆脂瘤中的血管生成因子及其调节转录因子进行了分析。人皮肤角质形成细胞和上皮细胞用于评估候选转录因子对血管生成因子调节和内皮细胞增殖的影响。地点:大学耳鼻咽喉-头颈外科。参加者:使用了8个临床胆囊解剖标本和8个对照标本进行细胞和分子生物学评估。另外的8个胆囊解剖和8个听觉皮肤样本被用于微阵列研究。主要观察指标:通过化学方法和分子生物学方法对血管内皮生长因子,白介素8和环氧合酶2的表达进行了测定。结果:人耳胆总管标本在胆总管基质和周围基质中表达丰富的血管生成因子,例如血管内皮生长因子,并伴有DNA结合的转录因子抑制剂(Id1)。我们发现Id1是血管内皮生长因子的重要调节剂。此外,有效的血管生成因子,包括白介素8和环氧合酶2,是由Idl通过不同的分子机制调节的。结论和相关性:转录因子Idl通过调节血管内皮生长因子,白介素8和环氧合酶2来控制胆脂瘤的血管生成,所述血管内皮生长因子,白介素8和环氧合酶2负责胆脂瘤的血管生成。 Idl可以作为治疗中耳环境中胆总动脉进展的良好靶标。

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