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Role of Extracellular Signal-Regulated Kinase, p38 Kinase, and Activator Protein-1 in Transforming Growth Factor-β1–Induced Alpha Smooth Muscle Actin Expression in Human Fetal Lung Fibroblasts In Vitro

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Abstract

Myofibroblasts characterized by alpha smooth muscle actin(α-SMA) expression play a key role in pulmonary fibrosis. Transforming growth factor-beta1 (TGF-β1) is likely to be involved in the emergence of myofibroblasts, but the intracellular signal pathways for this process have not been well determined. The aim of the present study was to investigate the role of mitogen-activated protein kinase (MAPK)/activator protein-1 (AP-1) signaling pathways in TGF-β1–induced α-SMA expression in human fetal lung fibroblasts (HLF-02). We found that TGF-β1 treatment activated p38 kinase and extracellular signal-regulated kinase (Erk) in HLF-02 cells. The induction of α-SMA by TGF-β1 was suppressed by p38 kinase inhibitor (SB203580) and Erk inhibitor (PD98059). AP-1 inhibitor curcumin also inhibited TGF-β1–induced α-SMA expression. In addition, dominant negative mutant c-Jun (TAM67) downregulated TGF-β1–induced AP-1 transactivation and α-SMA expression. In additional, PD98059 but not SB203580 inhibited the AP-1 DNA binding activity induced by TGF-β1. Based on these findings, we conclude that p38 kinase, Erk, and AP-1 are responsible for the α-SMA expression induced by TGF-β1 in human fetal lung fibroblasts. Erk is involved in inducing α-SMA expression via AP-1 activation.

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Acknowledgments

The authors thank Prof. Wen Ji-Fang for his expert technical support and valuable discussions. This work was supported by the National Natural Science Foundation of China (No. 30170399).

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Authors and Affiliations

  1. Department of Pathology, Xiangya Medical School, Central South University, Tong Zi Po Road 172, Changsha, 410013, China

    Yongbin Hu, Jinwu Peng, Deyun Feng, Ling Chu, Xiang Li, Zhongyuan Jin, Zhi Lin & Qingfu Zeng

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  1. Yongbin Hu
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  2. Jinwu Peng
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  8. Qingfu Zeng
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Correspondence to Qingfu Zeng.

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Hu, Y., Peng, J., Feng, D. et al. Role of Extracellular Signal-Regulated Kinase, p38 Kinase, and Activator Protein-1 in Transforming Growth Factor-β1–Induced Alpha Smooth Muscle Actin Expression in Human Fetal Lung Fibroblasts In Vitro. Lung 184, 33–42 (2006). https://doi.org/10.1007/s00408-005-2560-5

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