Department of Otolaryngology, The Second hospital, Cheeloo College of Medicine, Shandong University, 274 Beiyuan Road, Jinan, Shandong, China; National Health Commission Key Laboratory of Otolaryngology, The Second hospital, Cheeloo College of Medicine, Shandong University, 274 Beiyuan Road, Jinan, Shandong, China.
Hearing reconstruction Key Laboratory of Shandong province/Central Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 324 Jingwu Weiqi Road, Jinan, Shandong, China; Institute of Medical Sciences, The Second Hospital of Shandong University, Shandong University, 274 Beiyuan Road, Jinan, Shandong, China.
Biochem Biophys Res Commun. 2021 Feb 12;540:95-100. doi: 10.1016/j.bbrc.2020.12.052. Epub 2021 Jan 13.
Acquired middle ear cholesteatoma leads to hearing loss, ear discharge, ear pain, and more serious intracranial complications. However, there is still no effective treatment other than surgery. TFIIB-related factor 2 (BRF2) acted as a redox sensor overexpressing in oxidative stress which linked endoplasmic reticulum (ER) stress, while glucose-regulated protein 78 (GRP78) was a biomarker of ER stress in cancer, atherosclerosis and inflammation. In our study, we investigated the roles of BRF2 and GRP78 in acquired middle ear cholesteatoma. Our results revealed that the expression of BRF2 was significant increased in acquired middle ear cholesteatoma, and which was positively correlated with the expression of GRP78. In addition, BRF2 and GRP78 showed colocalization in epithelium of acquired middle ear cholesteatomas and HaCaT cells. Prolongation of LPS stimulation in HaCaT cells escalated the expression of BRF2 and GRP78. To confirm the role of BRF2 and GRP78, we transfected si-BRF2 into HaCaT cells. All results indicated that BRF2 expression positively regulates the expression of GRP78 and may participate in the pathogenesis of acquire middle ear cholesteatoma.
获得性中耳胆脂瘤可导致听力损失、耳漏、耳痛，甚至更严重的颅内并发症。然而，除了手术之外，目前尚无有效的治疗方法。TFIIB 相关因子 2（BRF2）作为一种在氧化应激中过度表达的氧化还原传感器，与内质网（ER）应激相关，而葡萄糖调节蛋白 78（GRP78）是癌症、动脉粥样硬化和炎症中 ER 应激的生物标志物。在我们的研究中，我们研究了 BRF2 和 GRP78 在获得性中耳胆脂瘤中的作用。我们的结果表明，BRF2 的表达在获得性中耳胆脂瘤中显著增加，并且与 GRP78 的表达呈正相关。此外，BRF2 和 GRP78 在获得性中耳胆脂瘤和 HaCaT 细胞的上皮中存在共定位。延长 LPS 刺激 HaCaT 细胞可上调 BRF2 和 GRP78 的表达。为了证实 BRF2 和 GRP78 的作用，我们将 si-BRF2 转染到 HaCaT 细胞中。所有结果均表明，BRF2 表达可正向调节 GRP78 的表达，并可能参与获得性中耳胆脂瘤的发病机制。
