单位：[1]Department of Otolaryngology-Head and Neck Surgery,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,China华中科技大学同济医学院附属同济医院耳鼻咽喉-头颈外科[2]Hepatic Surgery Center,Tongji Hospital,Tongji Medical College,Huazhong外科学系肝脏外科华中科技大学同济医学院附属同济医院[3]Clinical Medical Research Center of Hepatic Surgery at Hubei Province, Wuhan, China[4]Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College,Huazhong University of Science and Technology, Wuhan, China[5]Division of Allergy-Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA[6]Department of Otolaryngology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA[7]Department of Immunology, School of Basic Medicine, Tongji Medical College,Huazhong University of Science and Technology, Wuhan, China[8]Cell Architecture Research 23 Center, Huazhong University of Science and Technology, Wuhan, China
Although the expression of Mex3 RNA binding family member B (MEX3B) is upregulated in human nasal epithelial cells (HENCs) predominately in the eosinophilic chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) subtype, its functions as an RNA binding protein in airway epithelial cells remain unknown. Here, we revealed the role of MEX3B based on different subtypes of CRS, and demonstrated that MEX3B decreased TGF-β receptor III (TGFBR3) mRNA level by binding to its 3' UTR and reducing its stability in HNECs. TGF-βR3 was found to be a TGF-β2 specific coreceptor in HNECs. Knocking down or overexpressing MEX3B promoted or inhibited TGF-β2-induced phosphorylation of Smad2 in HNECs, respectively. TGF-βR3 and p-Smad2 levels were downregulated in CRSwNP compared with controls and CRS without nasal polyps (CRSsNP), with a more prominent downregulation in the eosinophilic CRSwNP. TGF-β2 promoted collagen production in HNECs. Collagen abundance decreased and edema scores increased in CRSwNP compared to control, again more prominently in the eosinophilic type. Collagen expression in eosinophilic CRSwNP was negatively correlated with MEX3B but positively correlated with TGF-βR3. These results suggest that MEX3B inhibits tissue fibrosis in eosinophilic CRSwNP by downregulating epithelial cell TGFBR3 expression; consequently, MEX3B might be a valuable therapeutic target against eosinophilic CRSwNP.
基金：
This study was supported by the National Natural Science Foundation of China (NSFC) grants 81920108011, 82130030, and 81630024 (Z.L.), 82071026 (B.L.) and 82101199 (J.X.L), the National Key Research and Development Program of China 2022YFE0131200 (Z.L.), and the Key Research and Development Program of Hubei Province 2021BCA119 (Z.L.), and Grants AI137174 and PO1AI145818 (Chronic Rhinosinusitis Integrative Studies Program 2 (CRISP2)) from the NIH (R.P.S), and Tongji Hospital (HUST) Foundation for Excellent Young Scientist 2020YQ07 (B.L.)
第一作者单位：[1]Department of Otolaryngology-Head and Neck Surgery,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,China
共同第一作者：
通讯作者：
通讯机构：[1]Department of Otolaryngology-Head and Neck Surgery,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,China[7]Department of Immunology, School of Basic Medicine, Tongji Medical College,Huazhong University of Science and Technology, Wuhan, China[8]Cell Architecture Research 23 Center, Huazhong University of Science and Technology, Wuhan, China[*1]Department of Otolaryngology-Head and Neck Surgery,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,No. 1095 Jiefang Avenue,Wuhan 430030,China[*2]Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
推荐引用方式(GB/T 7714)：
Liu Jin-Xin,Ao-Nan Chen,Yu Qihong,et al.MEX3B inhibits collagen production in eosinophilic nasal polyps by downregulating epithelial cell TGFBR3 mRNA stability[J].JCI INSIGHT.2023,8(9):doi:10.1172/jci.insight.159058.
APA：
Liu Jin-Xin,Ao-Nan Chen,Yu Qihong,Shi Ke-Tai,Liu Yi-Bo...&Liu Zheng.(2023).MEX3B inhibits collagen production in eosinophilic nasal polyps by downregulating epithelial cell TGFBR3 mRNA stability.JCI INSIGHT,8,(9)
MLA：
Liu Jin-Xin,et al."MEX3B inhibits collagen production in eosinophilic nasal polyps by downregulating epithelial cell TGFBR3 mRNA stability".JCI INSIGHT 8..9(2023)
医学