TY - JOUR
T1 - SIRT6 inhibits TNF-α-induced inflammation of vascular adventitial fibroblasts through ROS and Akt signaling pathway
AU - He, Yanhao
AU - Xiao, Yunfang
AU - Yang, Xiaofeng
AU - Li, Yanxiang
AU - Wang, Bo
AU - Yao, Feng
AU - Shang, Chenxu
AU - Jin, Zhen
AU - Wang, Weirong
AU - Lin, Rong
N1 - Publisher Copyright:
© 2017 Elsevier Inc.
PY - 2017/8/1
Y1 - 2017/8/1
N2 - 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-α (TNF-α) 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-α-treated VAFs. In contrast, TNF-α 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-α-induced expression of MCP-1 and IL-6, respectively. Overexpression of SIRT1 and SIRT6 inhibited TNF-α-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-α-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-α-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-1β was increased in carotid collar-induced vascular inflammation. Taken together, these findings indicate that SIRT1 and SIRT6 inhibit TNF-α-induced inflammation in VAFs by ROS and Akt pathway.
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-α (TNF-α) 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-α-treated VAFs. In contrast, TNF-α 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-α-induced expression of MCP-1 and IL-6, respectively. Overexpression of SIRT1 and SIRT6 inhibited TNF-α-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-α-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-α-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-1β was increased in carotid collar-induced vascular inflammation. Taken together, these findings indicate that SIRT1 and SIRT6 inhibit TNF-α-induced inflammation in VAFs by ROS and Akt pathway.
KW - Inflammation
KW - SIRT1
KW - SIRT6
KW - Vascular adventitial fibroblasts
UR - https://www.scopus.com/pages/publications/85018398455
U2 - 10.1016/j.yexcr.2017.05.001
DO - 10.1016/j.yexcr.2017.05.001
M3 - 文章
C2 - 28477980
AN - SCOPUS:85018398455
SN - 0014-4827
VL - 357
SP - 88
EP - 97
JO - Experimental Cell Research
JF - Experimental Cell Research
IS - 1
ER -