Naringenin inhibits TNF-α induced VSMC proliferation and migration via induction of HO-1.
Vascular smooth muscle cell (VSMC) proliferation and migration, which is triggered by various inflammatory stimuli, contributes importantly to the pathogenesis of atherosclerosis and restenosis. Naringenin is a citrus flavonoid with both lipid-lowering and insulin-like properties. Here, we investigated whether naringenin affects TNF-α-induced VSMC proliferation and migration and if so, whether heme oxygenase-1 (HO-1) is involved. Rat VSMCs were treated with naringenin alone or in combination of TNF-α stimulation. We found that naringenin induced HO-1 mRNA and protein levels, as well as its activity, in VSMCs. Naringenin inhibited TNF-α-induced VSMC proliferation and migration in a dose-dependent manner. Mechanistic study demonstrated that naringenin prevented ERK/MAPK and Akt phosphorylation while left p38 MAPK and JNK unchanged. Naringenin also blocked the increase of ROS generation induced by TNF-α. More importantly, the specific HO-1 inhibitor ZnPP IX or HO-1 siRNA partially abolished the beneficial effects of naringenin on VSMCs. These results suggest that naringenin may serve as a novel drug in the treatment of these pathologies by inducing HO-1 expression/activity and subsequently decreasing VSMC proliferation and migration.
Jiangsu Key Laboratory for Molecular and Medical Biotechnology and College of Life Sciences, Nanjing Normal University, Nanjing 210046, China.
Siyu
S
Chen
Yan
Y
Ding
Weiwei
W
Tao
Wenxiang
W
Zhang
Tingming
T
Liang
Chang
C
Liu
D000818:Animals; D001483:Base Sequence; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D017931:DNA Primers; D004790:Enzyme Induction; D044950:Flavanones / Q000494:pharmacology*; D051547:Heme Oxygenase-1 / Q000096:biosynthesis*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000494:pharmacology
D017931:DNA Primers; D044950:Flavanones; D014409:Tumor Necrosis Factor-alpha; D051547:Heme Oxygenase-1; C005273:naringenin