PMID- 27153994
OWN - NLM
STAT- MEDLINE
DCOM- 20170413
LR  - 20220819
IS  - 1420-908X (Electronic)
IS  - 1023-3830 (Linking)
VI  - 65
IP  - 8
DP  - 2016 Aug
TI  - High glucose induced-macrophage activation through TGF-beta-activated kinase 1 
      signaling pathway.
PG  - 655-64
LID - 10.1007/s00011-016-0948-8 [doi]
AB  - OBJECTIVE AND DESIGN: Transforming growth factor-beta-activated kinase 1 (TAK1) 
      plays a pivotal role in innate immune responses and kidney disease, and is 
      critically involved in macrophage activation. However, there is a paucity of data 
      to explore the role of high glucose (HG) in the regulation of TAK1 signaling and 
      its functional role in macrophage activation. We assume that TAK1 signaling in 
      hyperglycemic condition could be a key factor leading to macrophage activation 
      and inflammation response. METHODS: Mice macrophages were seeded on a 96-well 
      cell culture plate; cell viability was tested after treatment with different 
      concentration of TAK1 inhibitors. Cells were divided into groups (OZ300; MC; NC; 
      HG; HG + OZ30, 100, 300 nM) and treated for given time course. Monocyte 
      chemotactic protein1(MCP-1) and tumor necrosis factor-alpha (TNF-alpha) mRNA levels were 
      evaluated by qRT-PCR. Flow cytometry and confocal microscopy are used to analyse 
      the activated macrophage induced by HG. Expression levels of p-TAK1, TAB 1, 
      p-JNK, p-p38MAPK, NF-kappaBpp65 were detected by western blot. Nuclear translocation 
      of NF-kappaBp65 was assessed by confocal microscopy. RESULTS: Our data revealed that 
      high glucose not only significantly increased macrophage activation and 
      subsequently abnormal high-expression of MCP-1 and TNF-alpha, but likewise remarkably 
      enhanced TAK1 activation, MAPK phosphorylation, NF-kappaB expression in macrophages. 
      Furthermore, pharmacological inhibition of TAK1 attenuated high glucose-triggered 
      signal pathways, macrophage activation and inflammatory cytokines in a simulated 
      diabetic environment. CONCLUSION: Our findings suggested that high glucose 
      activated macrophages mainly in TAK1/MAPKs and TAK1/NF-kappaB-dependent manners, 
      which lead to the polarization of macrophages towards a pro-inflammatory 
      phenotype, and finally lead to diabetic nephropathy. In sum, the study raises 
      novel data about the molecular mechanisms involved in the high glucose-mediated 
      inflammatory response in macrophages.
FAU - Xu, Xingxin
AU  - Xu X
AD  - Department of Nephrology, The First Affiliated Hospital, Anhui Medical 
      University, Hefei, Anhui, People's Republic of China.
FAU - Qi, Xiangming
AU  - Qi X
AD  - Department of Nephrology, The First Affiliated Hospital, Anhui Medical 
      University, Hefei, Anhui, People's Republic of China.
FAU - Shao, Yunxia
AU  - Shao Y
AD  - Department of Nephrology, The First Affiliated Hospital, Anhui Medical 
      University, Hefei, Anhui, People's Republic of China.
FAU - Li, Yuanyuan
AU  - Li Y
AD  - Department of Nephrology, The First Affiliated Hospital, Anhui Medical 
      University, Hefei, Anhui, People's Republic of China.
FAU - Fu, Xin
AU  - Fu X
AD  - Department of Nephrology, The First Affiliated Hospital, Anhui Medical 
      University, Hefei, Anhui, People's Republic of China.
FAU - Feng, Shiyao
AU  - Feng S
AD  - Department of Nephrology, The First Affiliated Hospital, Anhui Medical 
      University, Hefei, Anhui, People's Republic of China.
FAU - Wu, Yonggui
AU  - Wu Y
AD  - Department of Nephrology, The First Affiliated Hospital, Anhui Medical 
      University, Hefei, Anhui, People's Republic of China. wuyonggui@medmail.com.cn.
LA  - eng
PT  - Journal Article
DEP - 20160506
PL  - Switzerland
TA  - Inflamm Res
JT  - Inflammation research : official journal of the European Histamine Research 
      Society ... [et al.]
JID - 9508160
RN  - 0 (7-oxozeanol)
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (NF-kappa B)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 5W827M159J (Zearalenone)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.25 (MAP Kinase Kinase Kinases)
RN  - EC 2.7.11.25 (MAP kinase kinase kinase 7)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Animals
MH  - Chemokine CCL2/genetics
MH  - Glucose/pharmacology
MH  - Hyperglycemia/*metabolism
MH  - MAP Kinase Kinase Kinases/antagonists & inhibitors/*metabolism
MH  - Macrophage Activation/drug effects
MH  - Macrophages/drug effects/*metabolism
MH  - Male
MH  - Mice, Inbred C57BL
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - NF-kappa B/metabolism
MH  - Phosphorylation
MH  - RNA, Messenger/metabolism
MH  - Signal Transduction/drug effects
MH  - Tumor Necrosis Factor-alpha/genetics
MH  - Zearalenone/analogs & derivatives/pharmacology
OTO - NOTNLM
OT  - Diabetic nephropathy
OT  - High glucose
OT  - Inflammation
OT  - MAPKs
OT  - NF-kappaB
OT  - TAK1
EDAT- 2016/05/08 06:00
MHDA- 2017/04/14 06:00
CRDT- 2016/05/08 06:00
PHST- 2015/10/30 00:00 [received]
PHST- 2016/04/25 00:00 [accepted]
PHST- 2016/03/22 00:00 [revised]
PHST- 2016/05/08 06:00 [entrez]
PHST- 2016/05/08 06:00 [pubmed]
PHST- 2017/04/14 06:00 [medline]
AID - 10.1007/s00011-016-0948-8 [pii]
AID - 10.1007/s00011-016-0948-8 [doi]
PST - ppublish
SO  - Inflamm Res. 2016 Aug;65(8):655-64. doi: 10.1007/s00011-016-0948-8. Epub 2016 May 
      6.