骨蛋白驱动的部分上皮-间充质转化控制着中耳胆脂瘤的发展。

IF 4.3 3区 材料科学 Q1 ENGINEERING, ELECTRICAL & ELECTRONIC
Lingling Zeng, Li Xie, Jin Hu, Chao He, Aiguo Liu, Xiang Lu, Wen Zhou
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引用次数: 0

摘要

胆脂瘤是一种常见的中耳疾病。目前,手术切除是唯一的治疗方法,但患者面临复发的高风险。胆脂瘤的分子基础在很大程度上仍然未知。在这里,我们发现主要由分泌蛋白组成的骨化蛋白(OPN)在中耳胆脂瘤的发病过程中起着至关重要的作用。全局转录组分析显示,人胆脂瘤组织上皮特征丧失,免疫反应增强。中耳胆脂瘤的定量 RT-PCR 和免疫组化染色验证了上皮标志物的表达减少,以及间质标志物(包括 Vimentin 和 Fibronectin)的表达升高,但不包括 N-Cadherin、α-平滑肌肌动蛋白(α-SMA)或铁绒毛抑制蛋白 1(FSP1),这表明存在部分上皮-间质转化(EMT)状态。此外,人胆脂瘤组织中 OPN 的表达明显升高。用 OPN 处理可促进细胞增殖、存活和迁移,并导致永生人角质形成细胞的部分 EMT。重要的是,阻断 OPN 信号传导可明显改善 SD 大鼠的胆脂瘤样症状。我们的机理研究表明,AKT-锌指E盒结合同工酶2(ZEB2)轴介导了OPN的作用。总之,这些研究结果表明,以 OPN 信号传导为靶点是治疗中耳胆脂瘤的一种很有前景的策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Osteopontin-driven partial epithelial-mesenchymal transition governs the development of middle ear cholesteatoma.
Cholesteatoma is a common disease of the middle ear. Currently, surgical removal is the only treatment option and patients face a high risk of relapse. The molecular basis of cholesteatoma remains largely unknown. Here, we show that Osteopontin (OPN), a predominantly secreted protein, plays a crucial role in the development of middle ear cholesteatoma. Global transcriptome analysis revealed the loss of epithelial features and an enhanced immune response in human cholesteatoma tissues. Quantitative RT-PCR and immunohistochemical staining of middle ear cholesteatoma validated the reduced expression of epithelial markers, as well as the elevated expression of mesenchymal markers including Vimentin and Fibronectin, but not N-Cadherin, α-smooth muscle actin (α-SMA) or ferroptosis suppressor protein 1 (FSP1), indicating a partial epithelial-mesenchymal transition (EMT) state. Besides, the expression of OPN was significantly elevated in human cholesteatoma tissues. Treatment with OPN promoted cell proliferation, survival and migration and led to a partial EMT in immortalized human keratinocyte cells. Importantly, blockade of OPN signaling could remarkably improve the cholesteatoma-like symptoms in SD rats. Our mechanistic study demonstrated that the AKT-zinc finger E-box binding homeobox 2 (ZEB2) axis mediated the effects of OPN. Overall, these findings suggest that targeting the OPN signaling represents a promising strategy for the treatment of middle ear cholesteatoma.
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来源期刊
CiteScore
7.20
自引率
4.30%
发文量
567
期刊介绍: ACS Applied Electronic Materials is an interdisciplinary journal publishing original research covering all aspects of electronic materials. The journal is devoted to reports of new and original experimental and theoretical research of an applied nature that integrate knowledge in the areas of materials science, engineering, optics, physics, and chemistry into important applications of electronic materials. Sample research topics that span the journal's scope are inorganic, organic, ionic and polymeric materials with properties that include conducting, semiconducting, superconducting, insulating, dielectric, magnetic, optoelectronic, piezoelectric, ferroelectric and thermoelectric. Indexed/​Abstracted: Web of Science SCIE Scopus CAS INSPEC Portico
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