Identification of Id1 in Acquired Middle Ear Cholesteatoma

Zhang, Quan An; Hamajima, Yuki; Zhang, Qing; Lin, Jizhen

doi:10.1001/archotol.134.3.306

Cited by 20 publications

(19 citation statements)

References 13 publications

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“…First, Id1 is upregulated in the middle ear cholesteatomal specimens, as shown in recent studies. 12,13 Second, Id1 is able to increase the expression of VEGF, IL-8, and COX-2 in keratinocytes in vitro. Third, Id1 directly increases the proliferation of human endothelial cells.…”

Section: Discussionmentioning

confidence: 99%

“…20 The Id1 complementary DNA (cDNA) was constructed as previously described. 12 Short interfering RNA of Id1 and its control (nonspecific short interfering RNA) were constructed in a similar way, as previously described. 21 The p65 and p50 cDNA constructs were made as previously described.…”

Section: Cell Culturementioning

confidence: 99%

“…12,13 The presence of blood vessels in the cholesteatomal perimatrix is essential for the aggressive growth of cholesteatoma. Without the angiogenesis in the perimatrix, cholesteatoma grows but probably in a very limited manner.…”

Section: Commentmentioning

confidence: 99%

“…Our recent studies suggest that transcription factor inhibitor of DNA binding (Id1) is active in otitis media and the cholesteatomal perimatrix. 12,13 The role of Id1 in the activation of endothelial cells 14 and the angiogenesis of tumors 15,16 prompted us to study whether Id1 plays a role in the angiogenesis of cholesteatoma.…”

mentioning

confidence: 99%

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Regulation of the Angiogenesis of Acquired Middle Ear Cholesteatomas by Inhibitor of DNA Binding Transcription Factor

Fukudome

Wang

Hamajima

et al. 2013

JAMA Otolaryngol Head Neck Surg

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Importance:The aggressive growth of cholesteatoma in the middle ear involves the angiogenesis of the cholesteatomal 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 endothelial 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 otolaryngologyhead 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 cyclooxygenase 2 as measured by means of immunohistochemistry 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 Id1 via different molecular mechanisms. Conclusions and Relevance:The transcription factor Id1 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. Id1 may serve as a good target for the treatment of cholesteatomal progression in the middle ear milieu.

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Section: Discussionmentioning

confidence: 99%

Section: Cell Culturementioning

confidence: 99%

Section: Commentmentioning

confidence: 99%

mentioning

confidence: 99%

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Regulation of the Angiogenesis of Acquired Middle Ear Cholesteatomas by Inhibitor of DNA Binding Transcription Factor

Fukudome

Wang

Hamajima

et al. 2013

JAMA Otolaryngol Head Neck Surg

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“…VEGF is known to be involved in the pathogenesis of COM. Id1 also upregulates the activity of nuclear factor kappa B (NF-κB) in our previous studies [28][29][30][31]. NF-κB related chemokines, together with IL-6, attract lymphocytes at the stage of chronic infection [32].…”

Section: Chronic Infection Pd-l1/pd-1 and Immunotolerancementioning

confidence: 95%