PMID- 27289030
OWN - NLM
STAT- MEDLINE
DCOM- 20170907
LR  - 20171120
IS  - 1872-9142 (Electronic)
IS  - 0161-5890 (Linking)
VI  - 75
DP  - 2016 Jul
TI  - Targeted inhibition of GATA-6 attenuates airway inflammation and remodeling by 
      regulating caveolin-1 through TLR2/MyD88/NF-kappaB in murine model of asthma.
PG  - 144-50
LID - S0161-5890(16)30087-6 [pii]
LID - 10.1016/j.molimm.2016.05.017 [doi]
AB  - The purpose of this study was to evaluate the effects of GATA-6 on airway 
      inflammation and remodeling and the underlying mechanisms in a murine model of 
      chronic asthma. Female BALB/c mice were randomly divided into four groups: 
      phosphate-buffered saline control (PBS), ovalbumin (OVA)-induced asthma group 
      (OVA), OVA+ siNC and OVA+ siGATA-6. In this mice model, GATA-6 expression level 
      was significantly elevated and the expression in Caveolin-1 (Cav-1) inversely 
      correlated with the abundance of GATA-6 in OVA-induced asthma of mice. Silencing 
      of GATA-6 gene expression upregulated Cav-1 expression. Additionally, 
      downregulation of GATA-6 dramatically decreased OVA-challenged inflammation, 
      infiltration, and mucus production. Moreover, silencing of GATA-6 resulted in 
      decreased levels of immunoglobulin E (IgE) and inflammatory mediators and reduced 
      inflammatory cell accumulation, as well as inhibiting the expression of important 
      mediators including matrix metalloproteinase (MMP)-2 and MMP-9, TGF-beta1, and a 
      disintegrin and metalloproteinase 8 (ADAM8) and ADAM33, which is related to 
      airway remodeling. Further analysis confirmed that silencing of GATA-6 attenuated 
      OVA-induced airway inflammation and remodeling through the TLR2/MyD88 and NF-kappaB 
      pathway. In conclusion, these findings indicated that the downregulation of 
      GATA-6 effectively inhibited airway inflammation and reversed airway remodeling 
      via Cav-1, at least in part through downregulation of TLR2/MyD88/NF-kappaB, which 
      suggests that GATA-6 represents a promising therapeutic strategy for human 
      allergic asthma.
CI  - Copyright (c) 2016 Elsevier Ltd. All rights reserved.
FAU - Fang, Ping
AU  - Fang P
AD  - Respiratory Department, The Second Affiliated Hospital, Xi'an Jiaotong University 
      School of Medicine, Xi'an 710004, Shaanxi, PR China. Electronic address: 
      pingfangsx@163.com.
FAU - Shi, Hong-Yang
AU  - Shi HY
AD  - Respiratory Department, The Second Affiliated Hospital, Xi'an Jiaotong University 
      School of Medicine, Xi'an 710004, Shaanxi, PR China.
FAU - Wu, Xiao-Ming
AU  - Wu XM
AD  - Key Laboratory, Biochemical Information Engineering of Ministry of Education 
      Xi'an Jiaotong University School of Life Science and Technology, Xi'an 710049, 
      Shaanxi, PR China.
FAU - Zhang, Yong-Hong
AU  - Zhang YH
AD  - Respiratory Department, The Second Affiliated Hospital, Xi'an Jiaotong University 
      School of Medicine, Xi'an 710004, Shaanxi, PR China.
FAU - Zhong, Yu-Jie
AU  - Zhong YJ
AD  - Respiratory Department, The Second Affiliated Hospital, Xi'an Jiaotong University 
      School of Medicine, Xi'an 710004, Shaanxi, PR China.
FAU - Deng, Wen-Jing
AU  - Deng WJ
AD  - Respiratory Department, The Second Affiliated Hospital, Xi'an Jiaotong University 
      School of Medicine, Xi'an 710004, Shaanxi, PR China.
FAU - Zhang, Yu-Ping
AU  - Zhang YP
AD  - Respiratory Department, The Second Affiliated Hospital, Xi'an Jiaotong University 
      School of Medicine, Xi'an 710004, Shaanxi, PR China.
FAU - Xie, Mei
AU  - Xie M
AD  - Respiratory Department, The Second Affiliated Hospital, Xi'an Jiaotong University 
      School of Medicine, Xi'an 710004, Shaanxi, PR China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160609
PL  - England
TA  - Mol Immunol
JT  - Molecular immunology
JID - 7905289
RN  - 0 (Caveolin 1)
RN  - 0 (GATA6 Transcription Factor)
RN  - 0 (Gata6 protein, mouse)
RN  - 0 (Myd88 protein, mouse)
RN  - 0 (Myeloid Differentiation Factor 88)
RN  - 0 (NF-kappa B)
RN  - 0 (Tlr2 protein, mouse)
RN  - 0 (Toll-Like Receptor 2)
SB  - IM
MH  - Airway Remodeling/*immunology
MH  - Animals
MH  - Asthma/*immunology/metabolism
MH  - Blotting, Western
MH  - Caveolin 1/*biosynthesis/immunology
MH  - Disease Models, Animal
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Female
MH  - GATA6 Transcription Factor/*biosynthesis/immunology
MH  - Gene Expression Regulation/immunology
MH  - Gene Knockdown Techniques
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Myeloid Differentiation Factor 88/immunology/metabolism
MH  - NF-kappa B/immunology/metabolism
MH  - Polymerase Chain Reaction
MH  - Signal Transduction/*immunology
MH  - Toll-Like Receptor 2/immunology/metabolism
OTO - NOTNLM
OT  - Airway inflammation
OT  - Airway remodeling
OT  - Asthma
OT  - Caveolin-1 (Cav-1)
OT  - GATA-6
EDAT- 2016/06/12 06:00
MHDA- 2017/09/08 06:00
CRDT- 2016/06/12 06:00
PHST- 2016/03/26 00:00 [received]
PHST- 2016/05/20 00:00 [revised]
PHST- 2016/05/23 00:00 [accepted]
PHST- 2016/06/12 06:00 [entrez]
PHST- 2016/06/12 06:00 [pubmed]
PHST- 2017/09/08 06:00 [medline]
AID - S0161-5890(16)30087-6 [pii]
AID - 10.1016/j.molimm.2016.05.017 [doi]
PST - ppublish
SO  - Mol Immunol. 2016 Jul;75:144-50. doi: 10.1016/j.molimm.2016.05.017. Epub 2016 Jun 
      9.