PMID- 28100332
OWN - NLM
STAT- MEDLINE
DCOM- 20170726
LR  - 20211204
IS  - 1008-8830 (Print)
IS  - 1008-8830 (Linking)
VI  - 19
IP  - 1
DP  - 2017 Jan
TI  - [Expression and significance of mTOR/4EBP1/HIF-1alpha/VEGF signaling pathway in lung 
      tissues of asthmatic mice].
PG  - 104-110
AB  - OBJECTIVE: To study the expression and significance of the mammalian target of 
      rapamycin (mTOR)/eukaryote initiating factor 4E binding protein 1(4EBP1)/hypoxia 
      inducible factor-1alpha (HIF-1alpha)/vascular endothelial growth factor (VEGF) signaling 
      pathway in asthmatic mice. METHODS: Forty SPF level 6-8 week-old female Balb/C 
      mice were randomly divided into control, asthma, budesonide and mTOR inhibitor 
      (rapamycin) intervention groups (n=10 each). The asthmatic mouse model was 
      prepared via OVA induction and challenge test. The intervention groups were 
      administered with rapamycin at the dosage of 3 mg/kg by an intraperitoneal 
      injection or budesonide suspension at the dosage of l mg by aerosol inhalation 
      respectively 30 minutes before the OVA challenge. The control and asthma groups 
      were treated with normal saline instead. The concentrations of HIF-1alpha and VEGF in 
      bronchoalveolar lavage fluid (BALF) were examined using ELISA 24 hours after the 
      last challenge. The pathological changes of lung tissue were observed by 
      hematoxylin-eosin (HE) staining. The p-mTOR and p-4EBP1 from the lung tissues 
      were detected by immunohistochemistry and Western blot. Pearson analysis was used 
      to study the correlation between p-mTOR, p-4EBP1, HIF-1alpha, and VEGF expression. 
      RESULTS: Compared with the control group, inflammatory cell infiltration and 
      secretions in the trachea increased in the asthma group. The levels of HIF-1alpha and 
      VEGF in BALF and p-mTOR and p-4EBP1 expression in lung tissues also increased 
      (P<0.01). Compared with the asthma group, inflammatory cell infiltration and 
      secretions in the trachea were reduced in the two intervention groups, and the 
      levels of HIF-1alpha and VEGF in BALF and p-mTOR and p-4EBP1 expression in lung 
      tissues were also reduced (P<0.01). There were no significant differences in the 
      above changes between the two intervention groups and control group (P>0.05). In 
      the asthma group, there was a pairwise positive correlation between lung p-mTOR 
      and p-4EBP1 expression and HIF-1alpha and VEGF levels in BALF (P<0.05). However, 
      there were no correlations in the above indexes in the intervention groups and 
      control group. CONCLUSIONS: p-mTOR, p-4EBP1, HIF-1alpha and VEGF together are 
      involved in the pathogenesis of asthma. Rapamycin treatment can block this 
      signaling pathway, suggesting that this pathway can be used as a novel target for 
      asthma treatment.
FAU - Wang, Li
AU  - Wang L
AD  - Department of Pediatrics, Third Affiliated Hospital of Zhengzhou University, 
      Zhengzhou 450052, China. wxf456@126.com.
FAU - Zhang, Yan-Li
AU  - Zhang YL
FAU - Wang, Xiu-Fang
AU  - Wang XF
FAU - Song, Zhe
AU  - Song Z
FAU - Wang, Wei
AU  - Wang W
LA  - chi
PT  - Journal Article
PL  - China
TA  - Zhongguo Dang Dai Er Ke Za Zhi
JT  - Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics
JID - 100909956
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Carrier Proteins)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Eif4ebp1 protein, mouse)
RN  - 0 (Eukaryotic Initiation Factors)
RN  - 0 (Hif1a protein, mouse)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Phosphoproteins)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 0 (vascular endothelial growth factor A, mouse)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing
MH  - Animals
MH  - Asthma/drug therapy/*metabolism
MH  - Carrier Proteins/analysis/*physiology
MH  - Cell Cycle Proteins
MH  - Eukaryotic Initiation Factors
MH  - Female
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/analysis/*physiology
MH  - Lung/*chemistry/pathology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Phosphoproteins/analysis/*physiology
MH  - Signal Transduction/*physiology
MH  - TOR Serine-Threonine Kinases/analysis/*physiology
MH  - Vascular Endothelial Growth Factor A/analysis/*physiology
PMC - PMC7390129
EDAT- 2017/01/20 06:00
MHDA- 2017/07/27 06:00
PMCR- 2017/01/25
CRDT- 2017/01/20 06:00
PHST- 2017/01/20 06:00 [entrez]
PHST- 2017/01/20 06:00 [pubmed]
PHST- 2017/07/27 06:00 [medline]
PHST- 2017/01/25 00:00 [pmc-release]
AID - 10.7499/j.issn.1008-8830.2017.01.017 [pii]
AID - zgddekzz-19-1-104 [pii]
AID - 10.7499/j.issn.1008-8830.2017.01.017 [doi]
PST - ppublish
SO  - Zhongguo Dang Dai Er Ke Za Zhi. 2017 Jan;19(1):104-110. doi: 
      10.7499/j.issn.1008-8830.2017.01.017.