PMID- 37262956 OWN - NLM STAT- MEDLINE DCOM- 20230623 LR - 20230623 IS - 1878-1705 (Electronic) IS - 1567-5769 (Linking) VI - 120 DP - 2023 Jul TI - MiR-29a-3p promotes nasal epithelial barrier dysfunction via direct targeting of CTNNB1-VCL module in allergic rhinitis. PG - 110325 LID - S1567-5769(23)00648-3 [pii] LID - 10.1016/j.intimp.2023.110325 [doi] AB - Allergic rhinitis (AR) is resulted from immunoglobulin E (IgE)-mediated reactions to inhaled allergens which elicit mucosal inflammation and impair epithelial barrier integrity. However, whether miR-29a-3p as an epigenetic regulator that can contribute to epithelial barrier dysfunction in the pathogenesis of AR, and its underlying mechanism remians unclear. In this study, we discovered that miR-29a-3p was upregulated in AR patients and preferentially expressed in epithelial and glandular cells of nasal mucosa. VCL and CTNNB1, candidate target genes of miR-29a-3p, were predicted with several databases, including miRDB, miRanda, microT-CDS and TargetScan, and were validated through dual-luciferase reporter assay system. These two proteins were strongly associated with adherens junction (AJ) and tight junction (TJ) of nasal mucosa epithelial cells, in which played vital roles in mucosal integrity and nasal epithelial barrier function stability. Results for HNEpC culture and in vitro treatment experiments showed that expression of VCL and CTNNB1 were inhibited by miR-29a-3p mimic and were enhanced by miR-29a-3p inhibitor. In OVA-induced AR mice model, the expression pattern of miR-29a-3p and its target genes (Vcl and Ctnnb1) were consistent with the aforementioned quantitative results in AR patients, and miR-29a-3p antagomir could partially alleviate the symptom of OVA-induced AR in mice, restoring mucosal integrity and paracellular barrier function. In conclusion, our findings indicate that miR-29a-3p targets CTNNB1 and VCL to regulate nasal epithelial permeability and barrier function integrity, which may serve as a potential novel therapeutic target for the treatment of AR. CI - Copyright (c) 2023 Elsevier B.V. All rights reserved. FAU - Wang, Na AU - Wang N AD - Department of Otorhinolaryngology Head and Neck Surgery, XuanWu Hospital, Capital Medical University, No. 45, Changchun Street, Beijing 100053, PR China. FAU - Li, Pu AU - Li P AD - Department of Otorhinolaryngology Head and Neck Surgery, XuanWu Hospital, Capital Medical University, No. 45, Changchun Street, Beijing 100053, PR China. FAU - Liu, Junqi AU - Liu J AD - Department of Otorhinolaryngology Head and Neck Surgery, XuanWu Hospital, Capital Medical University, No. 45, Changchun Street, Beijing 100053, PR China. FAU - Wang, Zhenlin AU - Wang Z AD - Department of Otorhinolaryngology Head and Neck Surgery, XuanWu Hospital, Capital Medical University, No. 45, Changchun Street, Beijing 100053, PR China. Electronic address: wzl1812@163.com. LA - eng PT - Journal Article DEP - 20230530 PL - Netherlands TA - Int Immunopharmacol JT - International immunopharmacology JID - 100965259 RN - 0 (MicroRNAs) RN - 9006-59-1 (Ovalbumin) RN - 0 (MIRN29a microRNA, mouse) SB - IM MH - Animals MH - Mice MH - *MicroRNAs/genetics/metabolism MH - Nasal Mucosa/pathology MH - Ovalbumin/metabolism MH - *Rhinitis, Allergic/metabolism OTO - NOTNLM OT - Allergic rhinitis OT - CTNNB1 OT - Epithelial barrier OT - VCL OT - miR-29a-3p COIS- Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2023/06/02 01:07 MHDA- 2023/06/16 06:42 CRDT- 2023/06/01 18:01 PHST- 2023/02/17 00:00 [received] PHST- 2023/05/02 00:00 [revised] PHST- 2023/05/08 00:00 [accepted] PHST- 2023/06/16 06:42 [medline] PHST- 2023/06/02 01:07 [pubmed] PHST- 2023/06/01 18:01 [entrez] AID - S1567-5769(23)00648-3 [pii] AID - 10.1016/j.intimp.2023.110325 [doi] PST - ppublish SO - Int Immunopharmacol. 2023 Jul;120:110325. doi: 10.1016/j.intimp.2023.110325. Epub 2023 May 30.