Molecular Biology Reports

, Volume 39, Issue 4, pp 4597–4603 | Cite as

Ascochlorin suppresses TGF-β1-induced PAI-1 expression through the inhibition of phospho-EGFR in rat kidney fibroblast cells

  • Hyun-Ji Cho
  • Jeong-Han Kang
  • Ji-Hak Jeong
  • Yun-Jeong Jeong
  • Kwan-Kyu Park
  • Yoon-Yub Park
  • Yong-Suk Moon
  • Hong-Tae Kim
  • Il-Kyung Chung
  • Cheorl-Ho Kim
  • Hyeun-Wook Chang
  • Young-Chae Chang


Fibrosis is induced by the excessive and abnormal deposition of extracellular matrix (ECM) with various growth factors in tissues. Transforming growth factor-β1 (TGF-β1), the growth factor involved in fibrosis, modulates ECM synthesis and accumulation. TGF-β1 enhances the production of stimulators of ECM synthesis such as plasminogen activator inhibitor type 1 (PAI-1). As such, PAI-1 expression directly influences the proteolysis, invasion, and accumulation of ECM. It was shown in this study that ascochlorin, a prenylpenl antiobiotic, prevents the expression of profibrotic factors, such as PAI-1 and collagen type I, and that the TGF-β1-induced PAI-1 promoter activity is inhibited by ascochlorin. Ascochlorin abolishes the phosphorylation of the EGFR-MEK-ERK signaling pathway to regulate the TGF-β1-induced expression of PAI-1 without the inhibition of TβRII phosphorylation. Furthermore, the MEK inhibitor and EGFR siRNA block PAI-1 expression, and the Raf-1, MEK, and ERK signaling pathways for the regulation of PAI-1 expression. Ascochlorin suppresses the matrix metalloproteinases (MMPs) activity to activate the heparin-binding EGF-like growth factor (HB-EGF), to induce the phosphorylation of EGFR, and the MMPs inhibitor suppresses EGFR phosphorylation and the PAI-1 mRNA levels. These results suggest that ascochlorin prevents the expression of PAI-1 via the inhibition of an EGFR-dependent signal transduction pathway activated by MMPs.


Plasminogen activator inhibitor-1 Epidermal growth factor receptor Matrix metalloproteinase Ascochlorin Fibrosis 



Plasminogen activator inhibitor-1


Epidermal growth factor receptor


Matrix metalloproteinase


Transforming growth factor-β



This stuay was supported by the Grant of the Korean Ministry of Education, Science and Technology (The Regional Core Research Program/Anti-aging and Well-being Research Center).


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Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  • Hyun-Ji Cho
    • 1
  • Jeong-Han Kang
    • 1
  • Ji-Hak Jeong
    • 1
  • Yun-Jeong Jeong
    • 1
  • Kwan-Kyu Park
    • 1
  • Yoon-Yub Park
    • 1
  • Yong-Suk Moon
    • 1
  • Hong-Tae Kim
    • 1
  • Il-Kyung Chung
    • 2
  • Cheorl-Ho Kim
    • 3
  • Hyeun-Wook Chang
    • 4
  • Young-Chae Chang
    • 1
  1. 1.Research Institute of Biomedical Engineering and Department of MedicineCatholic University of Daegu School of MedicineDaeguRepublic of Korea
  2. 2.Department of BiotechnologyCatholic University of DaeguGyeongsanRepublic of Korea
  3. 3.Department of Biological ScienceSungkyunkwan UniversitySuwon, Kyunggi-DoRepublic of Korea
  4. 4.College of Pharmacy, Yeungnam UniversityGyeongsanRepublic of Korea

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