Dong Zihui, Jiang Yan, Zhang Jisheng, Zheng Chunge, Chen Han, Tang Wenrui, Yan Xudong, Yu Longgang, Han Lin, Wang Lin
Department of Otolaryngology-Head and Neck Surgery, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao 266100, China.
Medical Research Center, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao 266001, China.
Int Immunopharmacol. 2024 Dec 25;143(Pt 3):113545. doi: 10.1016/j.intimp.2024.113545. Epub 2024 Nov 2.
Epithelial-mesenchymal transition (EMT) is a key process of chronic rhinosinusitis with nasal polyps (CRSwNP). The molecular mechanism of EMT in CRSwNP remains unknown. In this study, we aimed to investigate the role of FERMT1 during the EMT process in CRSwNP.
Western blotting, qRT-PCR, and immunohistochemistry (IHC) were performed to examine the expression of related proteins and mRNAs. The migration ability of human nasal epithelial cells (HNEpCs) was evaluated with wound scratch assay. RNA sequencing was performed to investigate the downstream genes of FERMT1. The CRSwNP mouse model was established to study the effect of FERMT1 in vivo.
We found that FERMT1 was increased in nasal polyp tissues and correlated with the symptom scores of CRSwNP patients. Knockdown of FERMT1 inhibited the EMT process and cell migration induced by TGF-β1 through the PI3K/Akt pathway, and Akt inhibitor partially blocked the EMT induced by FERMT1 overexpression. In the CRSwNP mouse model, FERMT1 knockdown reduced nasal polyp formation and reversed the EMT process.
Our data indicate that knockdown of FERMT1 inhibits migration and EMT process of HNEpCs via PI3K/Akt signaling pathway, suggesting that FERMT1 may be a novel and potential therapeutic target for CRSwNP treatment.
上皮-间质转化（EMT）是慢性鼻-鼻窦炎伴鼻息肉（CRSwNP）的关键过程。CRSwNP中EMT的分子机制尚不清楚。在本研究中，我们旨在探讨FERMT1在CRSwNP的EMT过程中的作用。
采用蛋白质免疫印迹法、qRT-PCR和免疫组织化学（IHC）检测相关蛋白和mRNA的表达。采用划痕实验评估人鼻上皮细胞（HNEpCs）的迁移能力。进行RNA测序以研究FERMT1的下游基因。建立CRSwNP小鼠模型以研究FERMT1在体内的作用。
我们发现FERMT1在鼻息肉组织中表达增加，且与CRSwNP患者的症状评分相关。敲低FERMT1可通过PI3K/Akt途径抑制TGF-β1诱导的EMT过程和细胞迁移，Akt抑制剂可部分阻断FERMT1过表达诱导的EMT。在CRSwNP小鼠模型中，敲低FERMT1可减少鼻息肉形成并逆转EMT过程。
我们的数据表明，敲低FERMT1可通过PI3K/Akt信号通路抑制HNEpCs的迁移和EMT过程，提示FERMT1可能是CRSwNP治疗的一个新的潜在治疗靶点。
