PMID- 33980319
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210516
IS  - 2045-3701 (Print)
IS  - 2045-3701 (Electronic)
IS  - 2045-3701 (Linking)
VI  - 11
IP  - 1
DP  - 2021 May 12
TI  - The YAP/HIF-1alpha/miR-182/EGR2 axis is implicated in asthma severity through the 
      control of Th17 cell differentiation.
PG  - 84
LID - 10.1186/s13578-021-00560-1 [doi]
LID - 84
AB  - BACKGROUND: Asthma is a heterogeneous chronic inflammatory disease of the airway, 
      involving reversible airflow limitation and airway remodeling. T helper 17 (Th17) 
      cells play an important role in the pathogenesis of allergic asthma. However, 
      there is limited understanding of the signaling pathways controlling Th17 cell 
      differentiation in asthma. The aim of this study was to investigate if the 
      Yes-associated protein (YAP)/hypoxia inducible factor-1alpha (HIF-1alpha)/microRNA-182 
      (miR-182)/early growth response 2 (EGR2) axis is involved in mediating Th17 cell 
      differentiation and disease severity in asthma. METHODS: The study included 29 
      pediatric patients with asthma, 22 healthy volunteers, ovalbumin-induced murine 
      asthma models, and mouse naive CD4(+) T cells. The subpopulation of Th17 cells 
      was examined by flow cytometry. The levels of interleukin-17A were determined by 
      enzyme linked immunosorbent assay. Chromatin immunoprecipitation-quantitative 
      polymerase chain reaction assays and dual-luciferase reporter gene assays were 
      performed to examine interactions between HIF-1alpha and miR-182, and between miR-182 
      and EGR2. RESULTS: YAP, HIF-1alpha, and miR-182 were upregulated but EGR2 was 
      downregulated in human and mouse peripheral blood mononuclear cells from the 
      asthma group. Abundant expression of YAP and HIF-1alpha promoted miR-182 expression 
      and then inhibited EGR2, a target of miR-182, thus enhancing Th17 differentiation 
      and deteriorating asthma and lipid metabolism dysfunction. In addition, in vivo 
      overexpression of EGR2 countered the promoting effect of the YAP/HIF-1alpha/miR-182 
      axis on asthma and lipid metabolism dysfunction. CONCLUSION: These results 
      indicate that activation of the YAP/HIF-1alpha/miR-182/EGR2 axis may promote Th17 
      cell differentiation, exacerbate asthma development, and aggravate lipid 
      metabolism dysfunction, thus suggesting a potential therapeutic target for 
      asthma.
FAU - Zhou, Jing
AU  - Zhou J
AD  - Department of Respiratory Medicine, The First Affiliated Hospital of Nanchang 
      University, No. 17, Yongwai Street, Donghu District, Nanchang, 330006, People's 
      Republic of China.
FAU - Zhang, Ning
AU  - Zhang N
AD  - Department of Imaging, The First Affiliated Hospital of Nanchang University, 
      Nanchang, 330006, People's Republic of China.
FAU - Zhang, Wei
AU  - Zhang W
AD  - Department of Respiratory Medicine, The First Affiliated Hospital of Nanchang 
      University, No. 17, Yongwai Street, Donghu District, Nanchang, 330006, People's 
      Republic of China.
FAU - Lu, Caiju
AU  - Lu C
AD  - Department of Respiratory Medicine, The First Affiliated Hospital of Nanchang 
      University, No. 17, Yongwai Street, Donghu District, Nanchang, 330006, People's 
      Republic of China.
FAU - Xu, Fei
AU  - Xu F
AD  - Department of Respiratory Medicine, The First Affiliated Hospital of Nanchang 
      University, No. 17, Yongwai Street, Donghu District, Nanchang, 330006, People's 
      Republic of China. drFeiXuuue@163.com.
LA  - eng
GR  - 20192BAB205001/Natural Science Foundation of Jiangxi Province/
PT  - Journal Article
DEP - 20210512
PL  - England
TA  - Cell Biosci
JT  - Cell & bioscience
JID - 101561195
PMC - PMC8117288
OTO - NOTNLM
OT  - Asthma
OT  - Differentiation
OT  - Dyslipidemia
OT  - EGR2
OT  - HIF-1alpha
OT  - MiR-182
OT  - Th17 cells
OT  - YAP
COIS- The authors declare that they have no conflicts of interest.
EDAT- 2021/05/14 06:00
MHDA- 2021/05/14 06:01
PMCR- 2021/05/12
CRDT- 2021/05/13 05:38
PHST- 2020/08/19 00:00 [received]
PHST- 2021/02/18 00:00 [accepted]
PHST- 2021/05/13 05:38 [entrez]
PHST- 2021/05/14 06:00 [pubmed]
PHST- 2021/05/14 06:01 [medline]
PHST- 2021/05/12 00:00 [pmc-release]
AID - 10.1186/s13578-021-00560-1 [pii]
AID - 560 [pii]
AID - 10.1186/s13578-021-00560-1 [doi]
PST - epublish
SO  - Cell Biosci. 2021 May 12;11(1):84. doi: 10.1186/s13578-021-00560-1.