PMID- 28486191
OWN - NLM
STAT- MEDLINE
DCOM- 20180326
LR  - 20201209
IS  - 1950-6007 (Electronic)
IS  - 0753-3322 (Linking)
VI  - 91
DP  - 2017 Jul
TI  - NLRP4 is an essential negative regulator of fructose-induced cardiac injury in 
      vitro and in vivo.
PG  - 590-601
LID - S0753-3322(17)31267-2 [pii]
LID - 10.1016/j.biopha.2017.04.120 [doi]
AB  - High fructose consumption leads to metabolic syndrome and enhances cardiovascular 
      disease risk. However, our knowledge of the molecular mechanism underlying the 
      cardiac disease caused by fructose feeding is still poor. Nod-like receptors 
      (NLRs) are intracellular sensors, responding to a variety of intracellular danger 
      signals to induce injuries. NLRP4 is a negative regulator of nuclear factor-kappaB 
      (NF-kappaB) signaling pathway through interactions with kinase IkappaB kinase (IKK). 
      Here, we illustrated that NLRP4 attenuates pro-inflammatory cytokines releasing, 
      including Transforming growth factor (TGF-beta1), Tumor necrosis factor-alpha (TNF-alpha), 
      interleukin-1beta (IL-1beta), interleukin-18 (IL-18) and interleukin-6 (IL-6), in 
      fructose-treated cardiac cells by means of RT-qPCR, and western blotting 
      analysis. In addition, NLRP4 could reduce the expression of TANK-binding kinase 
      1/interferon regulatory factor 3 (TBK1/IRF3), reducing inflammation response and 
      achieving its anti-hypertrophic action. TBK1 plays critical roles in the IRF3 
      signaling pathway, modulating inflammation response. The inhibition of IKK/NF-kappaB 
      signaling pathway by NLRP4 is confirmed by NLRP4 over-expression and knockdown. 
      In vivo, high fructose feeding induced cardiac injury, accompanied with reduced 
      expression of NLRP4 in heart tissue samples, indicating the possible role of 
      NLRP4 in ameliorating heart injury. In conclusion, the findings above indicated 
      that NLRP4 is an important mediator of cardiac remodeling in vitro and in vivo 
      through negatively regulating TBK1/IRF3 and IKK/NF-kappaB signaling pathways, 
      indicating that NLRP4 might be a promising therapeutic target against cardiac 
      inflammation.
CI  - Copyright (c) 2017. Published by Elsevier Masson SAS.
FAU - Lian, Yong-Gang
AU  - Lian YG
AD  - Department of Emergency Internal Medicine, Linyi People's Hospital, Jiefang Road 
      27, Linyi, Shandong Province, 276003, China.
FAU - Zhao, Hai-Ying
AU  - Zhao HY
AD  - Department of Emergency Internal Medicine, Linyi People's Hospital, Jiefang Road 
      27, Linyi, Shandong Province, 276003, China.
FAU - Wang, Sheng-Ji
AU  - Wang SJ
AD  - Department of Emergency Internal Medicine, Linyi People's Hospital, Jiefang Road 
      27, Linyi, Shandong Province, 276003, China.
FAU - Xu, Qin-Liang
AU  - Xu QL
AD  - Department of Emergency Internal Medicine, Linyi People's Hospital, Jiefang Road 
      27, Linyi, Shandong Province, 276003, China.
FAU - Xia, Xiang-Jun
AU  - Xia XJ
AD  - Department of Emergency Internal Medicine, Linyi People's Hospital, Jiefang Road 
      27, Linyi, Shandong Province, 276003, China. Electronic address: 89745963@qq.com.
LA  - eng
PT  - Journal Article
DEP - 20170506
PL  - France
TA  - Biomed Pharmacother
JT  - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
JID - 8213295
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Cytokines)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Nlrp4 protein, mouse)
RN  - 30237-26-4 (Fructose)
RN  - EC 3.4.19.12 (Ubiquitin-Specific Proteases)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing
MH  - Animals
MH  - Cell Line
MH  - Cytokines/metabolism
MH  - Down-Regulation
MH  - Feeding Behavior
MH  - Fructose
MH  - Gene Knockdown Techniques
MH  - Heart Injuries/*chemically induced/genetics/*metabolism
MH  - Inflammation Mediators/metabolism
MH  - Mice, Inbred C57BL
MH  - Muscle Cells/metabolism
MH  - Myocardium/pathology
MH  - Rats
MH  - Signal Transduction
MH  - Ubiquitin-Specific Proteases/genetics/*metabolism
OTO - NOTNLM
OT  - Cardiac injury
OT  - IKK/NF-kappaB
OT  - Inflammation
OT  - NLRP4
OT  - TBK1/IRF3
EDAT- 2017/05/10 06:00
MHDA- 2018/03/27 06:00
CRDT- 2017/05/10 06:00
PHST- 2017/03/18 00:00 [received]
PHST- 2017/04/19 00:00 [revised]
PHST- 2017/04/27 00:00 [accepted]
PHST- 2017/05/10 06:00 [pubmed]
PHST- 2018/03/27 06:00 [medline]
PHST- 2017/05/10 06:00 [entrez]
AID - S0753-3322(17)31267-2 [pii]
AID - 10.1016/j.biopha.2017.04.120 [doi]
PST - ppublish
SO  - Biomed Pharmacother. 2017 Jul;91:590-601. doi: 10.1016/j.biopha.2017.04.120. Epub 
      2017 May 6.