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γ-Tocotrienol Inhibits TGF-β1-Induced Contractile Phenotype Expression of Human Airway Smooth Muscle Cells

γ-Tocotrienol Inhibits TGF-β1-Induced Contractile Phenotype Expression of Human Airway Smooth Muscle Cells

Takehito Fukushima, Akira Yamasaki, Tomoya Harada, Hiroki Chikumi, Masanari Watanabe, Ryota Okazaki, Miki Takata, Yasuyuki Hasegawa, Jun Kurai, Masaaki Yanai, Akihiro Yamamoto, Yuriko Sueda, Andrew J Halayko, etc.

Yonago Acta Med. 2017 Mar 9;60(1):16-23.

PMID: 28331417

Abstract:

Background:
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 effects in vivo and in 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.
Methods:
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.
Results:
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.
Conclusion:
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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP14101612	γ-Tocotrienol		14101-61-2	Price

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