PMID- 28477980
OWN - NLM
STAT- MEDLINE
DCOM- 20171003
LR  - 20220330
IS  - 1090-2422 (Electronic)
IS  - 0014-4827 (Linking)
VI  - 357
IP  - 1
DP  - 2017 Aug 1
TI  - SIRT6 inhibits TNF-alpha-induced inflammation of vascular adventitial fibroblasts 
      through ROS and Akt signaling pathway.
PG  - 88-97
LID - S0014-4827(17)30266-5 [pii]
LID - 10.1016/j.yexcr.2017.05.001 [doi]
AB  - SIRT6, with both deacetylase and ADP-ribosyltransferase activities, is 
      predominantly expressed in the nucleus. It has been revealed that SIRT6 regulates 
      various biological functions including metabolism, aging and stress resistance. 
      This study aims to investigate the role of SIRT6 in vascular inflammation and it 
      molecular mechanism. We found that tumor necrosis factor-alpha (TNF-alpha) did not alter 
      the localization of SIRT6 in vascular adventitial fibroblasts (VAFs), vascular 
      endothelial cells (VECs) and vascular smooth muscle cells (VSMCs). The expression 
      of SIRT1, SIRT6 was decreased in TNF-alpha-treated VAFs. In contrast, TNF-alpha 
      significantly increased the expression of monocyte chemotactic protein 1 (MCP-1) 
      and interleukin (IL) -6. Knockdown of SIRT1 and SIRT6 by siRNA significantly 
      enhanced TNF-alpha-induced expression of MCP-1 and IL-6, respectively. Overexpression 
      of SIRT1 and SIRT6 inhibited TNF-alpha-induced expression of MCP-1 and IL-6 in VAFs. 
      Moreover, we also found SIRT1 positively regulated the expression of SIRT6 in 
      VAFs. In addition, knockdown of SIRT1 and SIRT6 respectively augmented 
      TNF-alpha-induced generation of reactive oxygen species (ROS) and phosphorylation of 
      protein kinase B (Akt). ROS scavenger N-acetyl-L-cysteine (NAC) and Akt inhibitor 
      MK2206 reduced TNF-alpha-induced mRNA expression of MCP-1 and IL-6 in VAFs. In vivo 
      studies indicated that the expression of SIRT1, SIRT6 was decreased and the 
      expression of MCP-1, IL-6 and IL-1beta was increased in carotid collar-induced 
      vascular inflammation. Taken together, these findings indicate that SIRT1 and 
      SIRT6 inhibit TNF-alpha-induced inflammation in VAFs by ROS and Akt pathway.
CI  - Copyright (c) 2017 Elsevier Inc. All rights reserved.
FAU - He, Yanhao
AU  - He Y
AD  - Department of Pharmacology, Xi'an Jiaotong University, Health Science Center, 
      Xi'an, Shaanxi 710061, China.
FAU - Xiao, Yunfang
AU  - Xiao Y
AD  - Department of Pharmacology, Xi'an Jiaotong University, Health Science Center, 
      Xi'an, Shaanxi 710061, China.
FAU - Yang, Xiaofeng
AU  - Yang X
AD  - Department of Pharmacology, Xi'an Jiaotong University, Health Science Center, 
      Xi'an, Shaanxi 710061, China.
FAU - Li, Yanxiang
AU  - Li Y
AD  - Taizhou Polytechnic College, Taizhou, Jiangsu 225300, China.
FAU - Wang, Bo
AU  - Wang B
AD  - Department of Pharmacology, Xi'an Jiaotong University, Health Science Center, 
      Xi'an, Shaanxi 710061, China.
FAU - Yao, Feng
AU  - Yao F
AD  - Department of Pharmacology, Xi'an Jiaotong University, Health Science Center, 
      Xi'an, Shaanxi 710061, China.
FAU - Shang, Chenxu
AU  - Shang C
AD  - Department of Pharmacology, Xi'an Jiaotong University, Health Science Center, 
      Xi'an, Shaanxi 710061, China.
FAU - Jin, Zhen
AU  - Jin Z
AD  - Department of Pharmacology, Xi'an Jiaotong University, Health Science Center, 
      Xi'an, Shaanxi 710061, China.
FAU - Wang, Weirong
AU  - Wang W
AD  - Laboratory Animal Center, Xi'an Jiaotong University, Health Science Center, 
      Xi'an, Shaanxi 710061, China.
FAU - Lin, Rong
AU  - Lin R
AD  - Department of Pharmacology, Xi'an Jiaotong University, Health Science Center, 
      Xi'an, Shaanxi 710061, China. Electronic address: linrong63@aliyun.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170504
PL  - United States
TA  - Exp Cell Res
JT  - Experimental cell research
JID - 0373226
RN  - 0 (Interleukin-6)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 3.5.1.- (Sirtuins)
RN  - EC 3.5.1.- (sirtuin 6, rat)
SB  - IM
MH  - Animals
MH  - Endothelial Cells/metabolism
MH  - Fibroblasts/*drug effects/metabolism
MH  - Inflammation/chemically induced/metabolism
MH  - Interleukin-6/metabolism
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - Rats
MH  - Reactive Oxygen Species/*metabolism
MH  - Signal Transduction/*drug effects
MH  - Sirtuins/*metabolism
MH  - Tumor Necrosis Factor-alpha/metabolism/*pharmacology
OTO - NOTNLM
OT  - Inflammation
OT  - SIRT1
OT  - SIRT6
OT  - Vascular adventitial fibroblasts
EDAT- 2017/05/10 06:00
MHDA- 2017/10/04 06:00
CRDT- 2017/05/08 06:00
PHST- 2016/12/06 00:00 [received]
PHST- 2017/04/23 00:00 [revised]
PHST- 2017/05/02 00:00 [accepted]
PHST- 2017/05/10 06:00 [pubmed]
PHST- 2017/10/04 06:00 [medline]
PHST- 2017/05/08 06:00 [entrez]
AID - S0014-4827(17)30266-5 [pii]
AID - 10.1016/j.yexcr.2017.05.001 [doi]
PST - ppublish
SO  - Exp Cell Res. 2017 Aug 1;357(1):88-97. doi: 10.1016/j.yexcr.2017.05.001. Epub 
      2017 May 4.