γ-Tocotrienol Inhibits TGF-β1-Induced Contractile Phenotype Expression of Human Airway Smooth Muscle Cells.
Tocotrienols, members of the vitamin E family, exist in four different isoforms (α, β, γ and δ tocotrienol) that have can be protective against brain damage, as well as having anticancer effectsin vivoandin vitro. We have shown that γ-tocotrienol inhibits human airway smooth muscle cell proliferation and migration induced by platelet-derived growth factor (PDGF)-BB by suppressing RhoA activation. In this study, we tested whether γ-tocotrienol modulates transforming growth factor (TGF) -β-induced induction of human airway smooth muscle (ASM) into a contractile phenotype and concomitant synthesis of extracellular matrix proteins.



ASM cells were stimulated with TGF-β1 (2 ng/mL) for 48 hours and the effect of γ-tocotrienol (50 μM) on α-smooth muscle actin, fibronectin and collagen I expression was assessed using Western blotting. The signaling pathways involved in TGF-β1 stimulation were also investigated.



TGF-β1 increased α-smooth muscle actin, fibronectin and collagen Ⅰ abundance by 3- to 5-fold. This response was inhibited significantly by γ-tocotrienol. Furthermore, γ-tocotrienol suppressed RhoA activation, but did not affect Smad2 or Smad3 phosphorylation.



These results indicate that γ-tocotrienol has potential for benefit in modulating on airway remodeling in asthma, likely via a mechanism involving the suppression of TGF-β activation of RhoA.
Division of Medical Oncology and Molecular Respirology, Department of Multidisciplinary Internal Medicine, school of Medicine, Tottori University Faculty of Medicine, Yonago 683-8504, Japan.
Takehito
T
Fukushima
Division of Medical Oncology and Molecular Respirology, Department of Multidisciplinary Internal Medicine, school of Medicine, Tottori University Faculty of Medicine, Yonago 683-8504, Japan.
Akira
A
Yamasaki
Division of Medical Oncology and Molecular Respirology, Department of Multidisciplinary Internal Medicine, school of Medicine, Tottori University Faculty of Medicine, Yonago 683-8504, Japan.
Tomoya
T
Harada
Division of Medical Oncology and Molecular Respirology, Department of Multidisciplinary Internal Medicine, school of Medicine, Tottori University Faculty of Medicine, Yonago 683-8504, Japan.
Hiroki
H
Chikumi
Division of Medical Oncology and Molecular Respirology, Department of Multidisciplinary Internal Medicine, school of Medicine, Tottori University Faculty of Medicine, Yonago 683-8504, Japan.
Masanari
M
Watanabe
Division of Medical Oncology and Molecular Respirology, Department of Multidisciplinary Internal Medicine, school of Medicine, Tottori University Faculty of Medicine, Yonago 683-8504, Japan.
Ryota
R
Okazaki
Division of Medical Oncology and Molecular Respirology, Department of Multidisciplinary Internal Medicine, school of Medicine, Tottori University Faculty of Medicine, Yonago 683-8504, Japan.
Miki
M
Takata
Division of Medical Oncology and Molecular Respirology, Department of Multidisciplinary Internal Medicine, school of Medicine, Tottori University Faculty of Medicine, Yonago 683-8504, Japan.
Yasuyuki
Y
Hasegawa
Division of Medical Oncology and Molecular Respirology, Department of Multidisciplinary Internal Medicine, school of Medicine, Tottori University Faculty of Medicine, Yonago 683-8504, Japan.
Jun
J
Kurai
Division of Medical Oncology and Molecular Respirology, Department of Multidisciplinary Internal Medicine, school of Medicine, Tottori University Faculty of Medicine, Yonago 683-8504, Japan.
Masaaki
M
Yanai
Division of Medical Oncology and Molecular Respirology, Department of Multidisciplinary Internal Medicine, school of Medicine, Tottori University Faculty of Medicine, Yonago 683-8504, Japan.
Akihiro
A
Yamamoto
Division of Medical Oncology and Molecular Respirology, Department of Multidisciplinary Internal Medicine, school of Medicine, Tottori University Faculty of Medicine, Yonago 683-8504, Japan.
Yuriko
Y
Sueda
†Departments of Physiology and Pathophysiology, and Internal Medicine, University of Manitoba, Winnipeg, MB R3E 3P4 Canada.
Andrew J
AJ
Halayko
Division of Medical Oncology and Molecular Respirology, Department of Multidisciplinary Internal Medicine, school of Medicine, Tottori University Faculty of Medicine, Yonago 683-8504, Japan.
Eiji
E
Shimizu
airway smooth muscle; asthma; remodeling; vitamin E; γ-Tocotrienol