The role of inhibitor of DNA‐binding (Id1) in hyperproliferation of keratinocytes: the pathological basis for middle ear cholesteatoma from chronic otitis media

Hamajima, Yuki; Komori, Masahiro; Preciado, Diego; Choo, Dan I.; Moribe, Kazuho; Murakami, Shingo; Ondrey, Frank G.; Lin, Jizhen

doi:10.1111/j.1365-2184.2010.00695.x

Cited by 27 publications

(38 citation statements)

References 34 publications

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“…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%

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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: 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%

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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“…This cell line, originally documented by Boukamp et al (1988), is believed to be an appropriate cellular model of psoriasis based on previous reports (Farkas et al, 2001;Tencomnao et al, 2009;George et al, 2010;Saelee et al, 2011;Ronpirin and Tencomnao, 2012). Hamajima et al (2010) demonstrated the role of Id1 in the hyperproliferation of keratinocytes, possibly via the nuclear factor-kappa B signaling pathway. Notably, we revealed that the nuclear factorkappa B signaling network might be a target for antipsoriatic herbal drugs (Saelee et al, 2011).…”

Section: A B Discussionmentioning

confidence: 99%

“…Of great interest, Id1 was recently demonstrated to contribute to the hyperproliferation of keratinocytes via the enhancement of cell cycle progression, removal of cell cycle inhibition, and increase in keratin production (Hamajima et al, 2010). With regard to psoriasis, Id1 messenger RNA (mRNA) and protein levels were found to be highly expressed in psoriatic involved skin (Bjorntorp et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Dithranol downregulates expression of Id1 mRNA in human keratinocytes in vitro

Ronpirin¹,

Tencomnao²

2012

Genet. Mol. Res.

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ABSTRACT. The precise causes of psoriasis, a chronic skin disorder characterized by hyperproliferation of keratinocytes and incomplete keratinization, are unclear. It is known that expression of helix-loop-helix transcription factor Id1, which functions as an inhibitor of differentiation, is upregulated in psoriatic skin. We investigated the effect of the antipsoriatic drug dithranol on mRNA and protein expression levels of Id1 in the HaCaT keratinocyte cell line. Cultured HaCaT cells were treated with 0-0.5 µg/mL dithranol for 30 min. After 2 and 4 h, total cellular RNA and total proteins were isolated from HaCaT cells, and quantitative real-time reverse transcriptase (RT-PCR) and Western blot were used to determine the mRNA and protein levels of Id1, respectively. Changes in normalized Id1 mRNA levels were observed only after 4 h of dithranol treatment. There was reduced expression of Id1 mRNA transcripts in the HaCaT cells treated with 0.1 mg/mL dithranol, but the reduction was not significant. The expression of Id1 mRNA was significantly downregulated (almost 50%) when 0.25 or 0.5 mg/mL dithranol was applied to the HaCaT cells. However, the normalized Id1 protein levels were not significantly ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 11 (3): 3290-3297 (2012) Dithranol downregulates Id1 mRNA 3291affected. The molecular mechanisms underlying this finding should be investigated further to help determine the therapeutic action of this drug.

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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: 99%