PMID- 30808715
OWN - NLM
STAT- MEDLINE
DCOM- 20200220
LR  - 20200309
IS  - 1573-4935 (Electronic)
IS  - 0144-8463 (Print)
IS  - 0144-8463 (Linking)
VI  - 39
IP  - 3
DP  - 2019 Mar 29
TI  - Apc gene suppresses intracranial aneurysm formation and rupture through 
      inhibiting the NF-kappaB signaling pathway mediated inflammatory response.
LID - BSR20181909 [pii]
LID - 10.1042/BSR20181909 [doi]
AB  - Background: Intracranial aneurysm (IA) is a critical acquired cerebrovascular 
      disease that may cause subarachnoid hemorrhage, and nuclear factor-kappaB 
      (NF-kappaB)-mediated inflammation is involved in the pathogenesis of IA. Adenomatous 
      polyposis coli (Apc) gene is a tumor suppressor gene associated with both 
      familial and sporadic cancer. Herein, the purpose of our study is to validate 
      effect of Apc gene on IA formation and rupture by regulating the NF-kappaB signaling 
      pathway mediated inflammatory response. Methods: We collected IA specimens (from 
      incarceration of IA) and normal cerebral arteries (from surgery of traumatic 
      brain injury) to examine expression of Apc and the NF-kappaB signaling pathway 
      related factors (NF-kappaB p65 and IkappaBalpha). ELISA was used to determine levels of 
      monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-alpha), 
      interleukin (IL)-1beta (IL-1beta), and IL-6. IA model was established in rats, and 
      Apc-siRNA was treated to verify effect of Apc on IA formation and rupture. Next, 
      regulation of Apc on the NF-kappaB signaling pathway was investigated. Results: 
      Reduced expression of Apc and IkappaBalpha, and increased expression of NF-kappaB p65 were 
      found in IA tissues. MCP-1, TNF-alpha, IL-1beta, and IL-6 exhibited higher levels in 
      unruptured and ruptured IA, which suggested facilitated inflammatory responses. 
      In addition, the IA rats injected with Apc-siRNA showed further enhanced 
      activation of NF-kappaB signaling pathway, and up-regulated levels of MCP-1, TNF-alpha, 
      IL-1beta, IL-6, MMP-2, and MMP-9 as well as extent of p65 phosphorylation in IA. 
      Conclusion: Above all, Apc has the potential role to attenuate IA formation and 
      rupture by inhibiting inflammatory response through repressing the activation of 
      the NF-kappaB signaling pathway.
CI  - (c) 2019 The Author(s).
FAU - Lai, Xian-Liang
AU  - Lai XL
AUID- ORCID: 0000-0003-3959-4275
AD  - Department of Neurosurgery, The Second Affiliated Hospital of Nanchang 
      University, Nanchang 330006, China laixianliang_lxl@163.com.
FAU - Deng, Zhi-Feng
AU  - Deng ZF
AD  - Department of Neurosurgery, The Second Affiliated Hospital of Nanchang 
      University, Nanchang 330006, China.
FAU - Zhu, Xin-Gen
AU  - Zhu XG
AD  - Department of Neurosurgery, The Second Affiliated Hospital of Nanchang 
      University, Nanchang 330006, China.
FAU - Chen, Zhi-Hua
AU  - Chen ZH
AD  - Department of Neurosurgery, The Second Affiliated Hospital of Nanchang 
      University, Nanchang 330006, China.
LA  - eng
PT  - Journal Article
DEP - 20190326
PL  - England
TA  - Biosci Rep
JT  - Bioscience reports
JID - 8102797
RN  - 0 (Adenomatous Polyposis Coli Protein)
RN  - 0 (Cytokines)
RN  - 0 (NF-kappa B)
RN  - EC 2.7.11.10 (I-kappa B Kinase)
SB  - IM
MH  - Adenomatous Polyposis Coli Protein/*genetics/metabolism
MH  - Adult
MH  - Aged
MH  - Animals
MH  - Cytokines/*genetics/metabolism
MH  - Female
MH  - Humans
MH  - I-kappa B Kinase/genetics/metabolism
MH  - Inflammation/genetics/metabolism
MH  - Intracranial Aneurysm/*genetics/metabolism/pathology
MH  - Male
MH  - Middle Aged
MH  - NF-kappa B/*genetics/metabolism
MH  - Rats, Sprague-Dawley
MH  - Rupture, Spontaneous/*genetics/metabolism
MH  - Signal Transduction/*genetics
MH  - Young Adult
PMC - PMC6434386
OTO - NOTNLM
OT  - Apc gene
OT  - Inflammatory response
OT  - Intracranial aneurysm
OT  - NF-kappaB signaling pathway
COIS- The authors declare that there are no competing interests associated with the 
      manuscript.
EDAT- 2019/02/28 06:00
MHDA- 2020/02/23 06:00
PMCR- 2019/03/26
CRDT- 2019/02/28 06:00
PHST- 2018/10/21 00:00 [received]
PHST- 2019/02/14 00:00 [revised]
PHST- 2019/02/19 00:00 [accepted]
PHST- 2019/02/28 06:00 [pubmed]
PHST- 2020/02/23 06:00 [medline]
PHST- 2019/02/28 06:00 [entrez]
PHST- 2019/03/26 00:00 [pmc-release]
AID - BSR20181909 [pii]
AID - 10.1042/BSR20181909 [doi]
PST - epublish
SO  - Biosci Rep. 2019 Mar 26;39(3):BSR20181909. doi: 10.1042/BSR20181909. Print 2019 
      Mar 29.