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MEX3B inhibits collagen production in eosinophilic nasal polyps by downregulating epithelial cell TGFBR3 mRNA stability
Although the expression of Mex3 RNA-binding family member B (MEX3B) is upregulated in human nasal epithelial cells (HNECs) predominately in the eosinophilic chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) subtype, its functions as an RNA binding protein in airway epithelial cells remain unkn...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Clinical Investigation
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10243817/ https://www.ncbi.nlm.nih.gov/pubmed/36976645 http://dx.doi.org/10.1172/jci.insight.159058 |
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author | Liu, Jin-Xin Chen, Ao-Nan Yu, Qihong Shi, Ke-Tai Liu, Yi-Bo Guo, Cui-Lian Wang, Zhe-Zheng Yao, Yin Pan, Li Lu, Xiang Xu, Kai Wang, Heng Zeng, Ming Liu, Chaohong Schleimer, Robert P. Wu, Ning Liao, Bo Liu, Zheng |
author_facet | Liu, Jin-Xin Chen, Ao-Nan Yu, Qihong Shi, Ke-Tai Liu, Yi-Bo Guo, Cui-Lian Wang, Zhe-Zheng Yao, Yin Pan, Li Lu, Xiang Xu, Kai Wang, Heng Zeng, Ming Liu, Chaohong Schleimer, Robert P. Wu, Ning Liao, Bo Liu, Zheng |
author_sort | Liu, Jin-Xin |
collection | PubMed |
description | Although the expression of Mex3 RNA-binding family member B (MEX3B) is upregulated in human nasal epithelial cells (HNECs) 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 the 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 phosphorylated SMAD2 levels were downregulated in CRSwNP compared with controls and CRS without nasal polyps 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 with 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. |
format | Online Article Text |
id | pubmed-10243817 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Society for Clinical Investigation |
record_format | MEDLINE/PubMed |
spelling | pubmed-102438172023-06-07 MEX3B inhibits collagen production in eosinophilic nasal polyps by downregulating epithelial cell TGFBR3 mRNA stability Liu, Jin-Xin Chen, Ao-Nan Yu, Qihong Shi, Ke-Tai Liu, Yi-Bo Guo, Cui-Lian Wang, Zhe-Zheng Yao, Yin Pan, Li Lu, Xiang Xu, Kai Wang, Heng Zeng, Ming Liu, Chaohong Schleimer, Robert P. Wu, Ning Liao, Bo Liu, Zheng JCI Insight Research Article Although the expression of Mex3 RNA-binding family member B (MEX3B) is upregulated in human nasal epithelial cells (HNECs) 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 the 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 phosphorylated SMAD2 levels were downregulated in CRSwNP compared with controls and CRS without nasal polyps 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 with 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. American Society for Clinical Investigation 2023-05-08 /pmc/articles/PMC10243817/ /pubmed/36976645 http://dx.doi.org/10.1172/jci.insight.159058 Text en © 2023 Liu et al. https://creativecommons.org/licenses/by/4.0/This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Research Article Liu, Jin-Xin Chen, Ao-Nan Yu, Qihong Shi, Ke-Tai Liu, Yi-Bo Guo, Cui-Lian Wang, Zhe-Zheng Yao, Yin Pan, Li Lu, Xiang Xu, Kai Wang, Heng Zeng, Ming Liu, Chaohong Schleimer, Robert P. Wu, Ning Liao, Bo Liu, Zheng MEX3B inhibits collagen production in eosinophilic nasal polyps by downregulating epithelial cell TGFBR3 mRNA stability |
title | MEX3B inhibits collagen production in eosinophilic nasal polyps by downregulating epithelial cell TGFBR3 mRNA stability |
title_full | MEX3B inhibits collagen production in eosinophilic nasal polyps by downregulating epithelial cell TGFBR3 mRNA stability |
title_fullStr | MEX3B inhibits collagen production in eosinophilic nasal polyps by downregulating epithelial cell TGFBR3 mRNA stability |
title_full_unstemmed | MEX3B inhibits collagen production in eosinophilic nasal polyps by downregulating epithelial cell TGFBR3 mRNA stability |
title_short | MEX3B inhibits collagen production in eosinophilic nasal polyps by downregulating epithelial cell TGFBR3 mRNA stability |
title_sort | mex3b inhibits collagen production in eosinophilic nasal polyps by downregulating epithelial cell tgfbr3 mrna stability |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10243817/ https://www.ncbi.nlm.nih.gov/pubmed/36976645 http://dx.doi.org/10.1172/jci.insight.159058 |
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