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γ-Tocotrienol Inhibits TGF-β1-Induced Contractile Phenotype Expression of Human Airway Smooth Muscle Cells
Takehito Fukushima1, Akira Yamasaki1, Tomoya Harada1
1Division of Medical Oncology and Molecular Respirology, Department of Multidisciplinary Internal Medicine, school of Medicine, Tottori University Faculty of Medicine, Yonago 683-8504, Japan.
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.
Insights
Gamma-tocotrienol, a vitamin E form, may benefit asthma by inhibiting airway remodeling. It suppresses transforming growth factor-beta (TGF-β) activation of RhoA, reducing airway smooth muscle cell changes.
Area of Science:
- Biochemistry
- Cell Biology
- Pharmacology
Background:
- Tocotrienols, vitamin E isoforms, show neuroprotective and anticancer properties.
- Gamma-tocotrienol inhibits PDGF-BB-induced airway smooth muscle cell proliferation and migration via RhoA suppression.
- This study investigates gamma-tocotrienol's effect on TGF-β-induced airway smooth muscle cell changes.
Purpose of the Study:
- To determine if gamma-tocotrienol modulates TGF-β-induced airway smooth muscle cell (ASM) differentiation.
- To assess the impact of gamma-tocotrienol on extracellular matrix protein synthesis in ASM cells.
- To explore the signaling pathways involved in TGF-β-induced ASM remodeling and gamma-tocotrienol's influence.
Main Methods:
- Human airway smooth muscle cells were stimulated with TGF-β1.
- The effects of gamma-tocotrienol on α-smooth muscle actin, fibronectin, and collagen I expression were analyzed via Western blotting.
- Signaling pathways, including RhoA, Smad2, and Smad3, were investigated.
Main Results:
- TGF-β1 significantly increased α-smooth muscle actin, fibronectin, and collagen I levels (3-5 fold).
- Gamma-tocotrienol administration markedly inhibited these TGF-β1-induced increases.
- Gamma-tocotrienol suppressed RhoA activation but did not affect Smad2 or Smad3 phosphorylation.
Conclusions:
- Gamma-tocotrienol demonstrates potential in mitigating airway remodeling in asthma.
- The mechanism likely involves the suppression of TGF-β-induced RhoA activation by gamma-tocotrienol.
- Further research into gamma-tocotrienol for asthma treatment is warranted.
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