PMID- 36072399
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220910
IS  - 1741-427X (Print)
IS  - 1741-4288 (Electronic)
IS  - 1741-427X (Linking)
VI  - 2022
DP  - 2022
TI  - Influences of miR-378a-3p on the Pathogenesis of Allergic Rhinitis via 
      GzmB-Mediated Inflammatory Reaction.
PG  - 5926834
LID - 10.1155/2022/5926834 [doi]
LID - 5926834
AB  - METHODS: Totally, 24 BALB/c mice were assigned to the AR group, control group, 
      GzmB group, and blank group (each n = 6). The blank group was normally fed 
      without treatment, and the other three groups were treated by ovalbumin (OVA) to 
      induce AR models, in which the GzmB group was intranasally injected with 
      lentiviral vector suppressing GzmB expression during the second immunization, 
      while the control group was given the GzmB-blank vector. The times of AR 
      pathological behaviours such as sneezing and scratching the nose of mice were 
      observed and counted. The nasal lavage fluid of each mouse was acquired, and 
      then, the mouse was executed by cervical dislocation, followed by collection of 
      blood and nasal mucosa tissues. Then, ELISA was adopted for quantifying 
      immunoglobulin E (IgE), interleukin (IL)-4, IL-6, and histamine (HA), and nasal 
      mucosa tissues were treated by HE and TUNEL staining to observing their 
      histopathological manifestations. PCR and western blot (WB) were adopted for 
      quantifying GzmB and miR-378a-3p. Additionally, with NP69 cells, dual luciferase 
      reporter (DLR) assay was carried out for determining the targeting association of 
      GzmB with miR-378a-3p. Another 24 mice were assigned to the AR group, GzmB group, 
      miR-378a-3p group, and GzmB+ miR-378a-3p group (each n = 6). The AR and GzmB 
      groups were treated as above. The miR-378a-3p group was intervened by lentiviral 
      vector suppressing miR-378a-3p, while the GzmB+ miR-378a-3p group was given GzmB 
      and lentiviral vector suppressing miR-378a-3p meantime. A rescue assay was 
      conducted through repeating the above tests. RESULTS: The times of sneezing and 
      rubbing the nose and the levels of IgE, IL-4, IL-6, and HA were similar between 
      the control and AR groups (all P > 0.05), and these items of the two groups were 
      all higher than those of the blank and GzmB groups (all P < 0.05). However, no 
      notable difference was observed in IL-4 and IL-6 levels between the GzmB and 
      blank groups (both P > 0.05), while higher levels of other detection results were 
      found in the former group than in the latter (all P < 0.05). The staining results 
      revealed obvious congestion, oedema, and necrosis structures in the nasal mucosa 
      epithelium of the control and AR groups and also revealed a large number of 
      infiltrating eosinophils and notable increase of apoptotic nasal mucosa 
      epithelial cells. The GzmB group showed notably improved nasal mucosa tissues, 
      and its infiltration and apoptosis of eosinophils were more notable than those of 
      the blank group, but notably weaker than those of the AR and control groups. 
      Additionally, the PCR and WB results revealed similar miR-378a-3p and GzmB levels 
      in nasal mucosa between the control and AR groups (both P > 0.05), and a notable 
      decrease of miR-378a-3p and a notable increase of GzmB in both groups (both P < 
      0.05). The DLR assay revealed notably suppressed fluorescence activity of GzmB-WT 
      in NP69 cells after transfection of miR-378a-3p mimics (P < 0.05) and notably 
      down regulated GzmB protein after increase of miR-378a-3p (P<0.05). Finally, the 
      rescue assay revealed that downregulating miR-378a-3p aggravated the pathological 
      changes of AR (P < 0.05) and also completely reversed the impacts of inhibiting 
      GzmB on the pathological behaviours of AR mice. CONCLUSIONS: MiR-378a-3p can 
      accelerate the pathological development of AR through targeted inhibition on the 
      release of pro-inflammatory factors such as IgE and HA activated by GzmB, so it 
      is a promising molecular target of AR therapy and offers a novel research 
      direction for the complete cure of AR.
CI  - Copyright (c) 2022 Xuping Wang et al.
FAU - Wang, Xuping
AU  - Wang X
AUID- ORCID: 0000-0002-0539-6214
AD  - Department of ENT, Affiliated Taikang Xianlin Drum Tower Hospital, Medical School 
      of Nanjing University, Nanjing, Jiangsu 210000, China.
FAU - Zhang, Haiqing
AU  - Zhang H
AD  - Department of ENT, Affiliated Taikang Xianlin Drum Tower Hospital, Medical School 
      of Nanjing University, Nanjing, Jiangsu 210000, China.
FAU - Du, Long
AU  - Du L
AD  - Department of ENT, Affiliated Taikang Xianlin Drum Tower Hospital, Medical School 
      of Nanjing University, Nanjing, Jiangsu 210000, China.
FAU - Zhang, Lian
AU  - Zhang L
AD  - Department of ENT, Affiliated Taikang Xianlin Drum Tower Hospital, Medical School 
      of Nanjing University, Nanjing, Jiangsu 210000, China.
LA  - eng
PT  - Journal Article
DEP - 20220829
PL  - United States
TA  - Evid Based Complement Alternat Med
JT  - Evidence-based complementary and alternative medicine : eCAM
JID - 101215021
PMC - PMC9444401
COIS- The authors declare that they have no conflicts of interest.
EDAT- 2022/09/09 06:00
MHDA- 2022/09/09 06:01
PMCR- 2022/08/29
CRDT- 2022/09/08 02:25
PHST- 2022/04/01 00:00 [received]
PHST- 2022/06/07 00:00 [revised]
PHST- 2022/06/22 00:00 [accepted]
PHST- 2022/09/08 02:25 [entrez]
PHST- 2022/09/09 06:00 [pubmed]
PHST- 2022/09/09 06:01 [medline]
PHST- 2022/08/29 00:00 [pmc-release]
AID - 10.1155/2022/5926834 [doi]
PST - epublish
SO  - Evid Based Complement Alternat Med. 2022 Aug 29;2022:5926834. doi: 
      10.1155/2022/5926834. eCollection 2022.