N-acetyl-l-cysteine inhibits TGF-β1-induced profibrotic responses in fibroblasts

Hisatoshi Sugiura, Tomohiro Ichikawa, Xiang-de Liu, Tetsu Kobayashi, Xing Qi Wang, Shin Kawasaki, Shinsaku Togo, Koichiro Kamio, Lijun Mao, Youngsoo Ann, Masakazu Ichinose, Stephen I. Rennard

Research output: Contribution to journalArticle

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Abstract

Background: Excessive production of TGF-β1 plays a key role in the tissue remodeling or fibrotic process observed in bronchial asthma, chronic pulmonary disease (COPD), and idiopathic pulmonary fibrosis (IPF). TGF-β1 has been reported to decrease the intracellular glutathione level and stimulate the production of reactive oxygen species. Objectives: The aim of this study was to evaluate whether the antioxidant N-acetyl-l-cysteine (NAC) can affect TGF-β1-mediated tissue remodeling in fibroblasts or modulate the production of fibronectin and vascular endothelial growth factor (VEGF) which are believed to be important mediators of tissue repair and remodeling. Methods: To accomplish this, human fetal lung fibroblasts (HFL-1) were used to assess the effect of NAC on the TGF-β1-mediated contraction of floating gels and the TGF-β1-induced mediator production. In addition, the effect of NAC on the TGF-β1-induced differentiation to myofibroblasts was evaluated by assessing α-smooth muscle actin (α-SMA) expression. Results: NAC significantly abolished the TGF-β1-augmented gel contraction (at 3 mM, gel size 63.4 ± 2.6% vs. 39.1 ± 4.1%; p < 0.01) compared with control in a concentration-dependent manner. NAC also significantly inhibited the TGF-β1-augmented fibronectin (p < 0.01) and VEGF (p < 0.01) production in the media of both the three-dimensional gel and monolayer culture. Furthermore, NAC reversed the TGF-β1-stimulated α-SMA expression (p < 0.01). Conclusion: These results suggest that NAC can affect the TGF-β1-induced tissue remodeling or fibrotic process in vitro.

Original languageEnglish (US)
Pages (from-to)487-491
Number of pages5
JournalPulmonary Pharmacology and Therapeutics
Volume22
Issue number6
DOIs
StatePublished - Dec 1 2009

Fingerprint

Acetylcysteine
Fibroblasts
Cysteine
Gels
Tissue
Fibronectins
Vascular Endothelial Growth Factor A
Idiopathic Pulmonary Fibrosis
Pulmonary diseases
Myofibroblasts
Lung Diseases
Glutathione
Smooth Muscle
Muscle
Actins
Monolayers
Reactive Oxygen Species
Repair
Chronic Disease
Asthma

Keywords

  • Collagen gel contraction
  • Fibronectin
  • Myofibroblast
  • Vascular endothelial growth factor

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Biochemistry, medical
  • Pharmacology (medical)

Cite this

Sugiura, H., Ichikawa, T., Liu, X., Kobayashi, T., Wang, X. Q., Kawasaki, S., ... Rennard, S. I. (2009). N-acetyl-l-cysteine inhibits TGF-β1-induced profibrotic responses in fibroblasts. Pulmonary Pharmacology and Therapeutics, 22(6), 487-491. https://doi.org/10.1016/j.pupt.2009.04.002

N-acetyl-l-cysteine inhibits TGF-β1-induced profibrotic responses in fibroblasts. / Sugiura, Hisatoshi; Ichikawa, Tomohiro; Liu, Xiang-de; Kobayashi, Tetsu; Wang, Xing Qi; Kawasaki, Shin; Togo, Shinsaku; Kamio, Koichiro; Mao, Lijun; Ann, Youngsoo; Ichinose, Masakazu; Rennard, Stephen I.

In: Pulmonary Pharmacology and Therapeutics, Vol. 22, No. 6, 01.12.2009, p. 487-491.

Research output: Contribution to journalArticle

Sugiura, H, Ichikawa, T, Liu, X, Kobayashi, T, Wang, XQ, Kawasaki, S, Togo, S, Kamio, K, Mao, L, Ann, Y, Ichinose, M & Rennard, SI 2009, 'N-acetyl-l-cysteine inhibits TGF-β1-induced profibrotic responses in fibroblasts', Pulmonary Pharmacology and Therapeutics, vol. 22, no. 6, pp. 487-491. https://doi.org/10.1016/j.pupt.2009.04.002
Sugiura, Hisatoshi ; Ichikawa, Tomohiro ; Liu, Xiang-de ; Kobayashi, Tetsu ; Wang, Xing Qi ; Kawasaki, Shin ; Togo, Shinsaku ; Kamio, Koichiro ; Mao, Lijun ; Ann, Youngsoo ; Ichinose, Masakazu ; Rennard, Stephen I. / N-acetyl-l-cysteine inhibits TGF-β1-induced profibrotic responses in fibroblasts. In: Pulmonary Pharmacology and Therapeutics. 2009 ; Vol. 22, No. 6. pp. 487-491.
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abstract = "Background: Excessive production of TGF-β1 plays a key role in the tissue remodeling or fibrotic process observed in bronchial asthma, chronic pulmonary disease (COPD), and idiopathic pulmonary fibrosis (IPF). TGF-β1 has been reported to decrease the intracellular glutathione level and stimulate the production of reactive oxygen species. Objectives: The aim of this study was to evaluate whether the antioxidant N-acetyl-l-cysteine (NAC) can affect TGF-β1-mediated tissue remodeling in fibroblasts or modulate the production of fibronectin and vascular endothelial growth factor (VEGF) which are believed to be important mediators of tissue repair and remodeling. Methods: To accomplish this, human fetal lung fibroblasts (HFL-1) were used to assess the effect of NAC on the TGF-β1-mediated contraction of floating gels and the TGF-β1-induced mediator production. In addition, the effect of NAC on the TGF-β1-induced differentiation to myofibroblasts was evaluated by assessing α-smooth muscle actin (α-SMA) expression. Results: NAC significantly abolished the TGF-β1-augmented gel contraction (at 3 mM, gel size 63.4 ± 2.6{\%} vs. 39.1 ± 4.1{\%}; p < 0.01) compared with control in a concentration-dependent manner. NAC also significantly inhibited the TGF-β1-augmented fibronectin (p < 0.01) and VEGF (p < 0.01) production in the media of both the three-dimensional gel and monolayer culture. Furthermore, NAC reversed the TGF-β1-stimulated α-SMA expression (p < 0.01). Conclusion: These results suggest that NAC can affect the TGF-β1-induced tissue remodeling or fibrotic process in vitro.",
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AU - Sugiura, Hisatoshi

AU - Ichikawa, Tomohiro

AU - Liu, Xiang-de

AU - Kobayashi, Tetsu

AU - Wang, Xing Qi

AU - Kawasaki, Shin

AU - Togo, Shinsaku

AU - Kamio, Koichiro

AU - Mao, Lijun

AU - Ann, Youngsoo

AU - Ichinose, Masakazu

AU - Rennard, Stephen I.

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N2 - Background: Excessive production of TGF-β1 plays a key role in the tissue remodeling or fibrotic process observed in bronchial asthma, chronic pulmonary disease (COPD), and idiopathic pulmonary fibrosis (IPF). TGF-β1 has been reported to decrease the intracellular glutathione level and stimulate the production of reactive oxygen species. Objectives: The aim of this study was to evaluate whether the antioxidant N-acetyl-l-cysteine (NAC) can affect TGF-β1-mediated tissue remodeling in fibroblasts or modulate the production of fibronectin and vascular endothelial growth factor (VEGF) which are believed to be important mediators of tissue repair and remodeling. Methods: To accomplish this, human fetal lung fibroblasts (HFL-1) were used to assess the effect of NAC on the TGF-β1-mediated contraction of floating gels and the TGF-β1-induced mediator production. In addition, the effect of NAC on the TGF-β1-induced differentiation to myofibroblasts was evaluated by assessing α-smooth muscle actin (α-SMA) expression. Results: NAC significantly abolished the TGF-β1-augmented gel contraction (at 3 mM, gel size 63.4 ± 2.6% vs. 39.1 ± 4.1%; p < 0.01) compared with control in a concentration-dependent manner. NAC also significantly inhibited the TGF-β1-augmented fibronectin (p < 0.01) and VEGF (p < 0.01) production in the media of both the three-dimensional gel and monolayer culture. Furthermore, NAC reversed the TGF-β1-stimulated α-SMA expression (p < 0.01). Conclusion: These results suggest that NAC can affect the TGF-β1-induced tissue remodeling or fibrotic process in vitro.

AB - Background: Excessive production of TGF-β1 plays a key role in the tissue remodeling or fibrotic process observed in bronchial asthma, chronic pulmonary disease (COPD), and idiopathic pulmonary fibrosis (IPF). TGF-β1 has been reported to decrease the intracellular glutathione level and stimulate the production of reactive oxygen species. Objectives: The aim of this study was to evaluate whether the antioxidant N-acetyl-l-cysteine (NAC) can affect TGF-β1-mediated tissue remodeling in fibroblasts or modulate the production of fibronectin and vascular endothelial growth factor (VEGF) which are believed to be important mediators of tissue repair and remodeling. Methods: To accomplish this, human fetal lung fibroblasts (HFL-1) were used to assess the effect of NAC on the TGF-β1-mediated contraction of floating gels and the TGF-β1-induced mediator production. In addition, the effect of NAC on the TGF-β1-induced differentiation to myofibroblasts was evaluated by assessing α-smooth muscle actin (α-SMA) expression. Results: NAC significantly abolished the TGF-β1-augmented gel contraction (at 3 mM, gel size 63.4 ± 2.6% vs. 39.1 ± 4.1%; p < 0.01) compared with control in a concentration-dependent manner. NAC also significantly inhibited the TGF-β1-augmented fibronectin (p < 0.01) and VEGF (p < 0.01) production in the media of both the three-dimensional gel and monolayer culture. Furthermore, NAC reversed the TGF-β1-stimulated α-SMA expression (p < 0.01). Conclusion: These results suggest that NAC can affect the TGF-β1-induced tissue remodeling or fibrotic process in vitro.

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KW - Myofibroblast

KW - Vascular endothelial growth factor

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