2. Academic Validation
  3. MEX3B inhibits collagen production in eosinophilic nasal polyps by downregulating epithelial cell TGFBR3 mRNA stability

MEX3B inhibits collagen production in eosinophilic nasal polyps by downregulating epithelial cell TGFBR3 mRNA stability

  • JCI Insight. 2023 Mar 28;e159058. doi: 10.1172/jci.insight.159058.
Jin-Xin Liu 1,  Chen Ao-Nan 1,  Qihong Yu 2,  Ke-Tai Shi 1,  Yi-Bo Liu 1,  Cui-Lian Guo 1,  Zhe-Zheng Wang 1,  Yin Yao 1,  Li Pan 1,  Xiang Lu 1,  Kai Xu 1,  Heng Wang 1,  Ming Zeng 1,  Chaohong Liu 3,  Robert P Schleimer 4,  Ning Wu 5,  Bo Liao 1,  Zheng Liu 1
Affiliations

Affiliations

  • 1 Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 2 Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 3 Department of Pathogen Biology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, China.
  • 4 Division of Allergy-Immunology, Department of Medicine, Feinberg School of Medicine Northwestern University, Chicago, United States of America.
  • 5 Department of Otolaryngology-Head and Neck Surgery, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, China.
PMID: 36976645 DOI: 10.1172/jci.insight.159058
Abstract

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.

Keywords

Allergy; Collagens; Inflammation.

Figures
Products