Connective tissue growth factor in hepatocytes is elevated by carbon tetrachloride via STAT3 activation

  • Authors:
    • Wenhsu Chen
    • Yingxiao Li
    • Chao‑Tien Hsu
    • Chiang‑Shan Niu
    • Wen‑Huang Pen
    • Kai‑Chun Cheng
    • Ho‑Shan Niu
  • View Affiliations

  • Published online on: January 8, 2020     https://doi.org/10.3892/mmr.2020.10916
  • Pages: 1390-1398
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Abstract

Carbon tetrachloride (CCl4) is widely used to induce hepatic fibrosis. Therapeutic agents alleviate hepatic fibrosis by inhibiting signal transducer and activator of transcription 3 (STAT3) activation. To understand the direct effects of CCl4 on STAT3 expression in the liver, the present study incubated cultured hepatocytes expressing connective tissue growth factor (CTGF) with CCl4. Rats exposed to CCl4 for 8 weeks exhibited hepatic fibrosis, which was confirmed through the assessment of plasma biomarkers. Isolated liver samples were used to determine the protein levels of CTGF and STAT3 using western blotting. In addition, STAT3 expression was silenced in α mouse liver 12 (AML‑12) cells using small interfering RNA transfection. In addition, a pharmacological inhibitor, stattic, was used to inhibit STAT3 expression. The incubation of AML‑12 cells with CCl4 induced a dose‑dependent increase in CTGF expression and STAT3 activation. Notably, silymarin, an extract from milk thistle, inhibited these changes in AML‑12 cells and the antioxidant tiron produced similar effects. Silencing of STAT3 reduced the CTGF expression promoted by CCl4 in the hepatocytes. Additionally, similar to tiron, stattic inhibited CTGF expression induced by CCl4. In conclusion, CCl4 may activate STAT3 through oxidative stress to promote CTGF expression, which is one of the main factors contributing to the risk of hepatic fibrosis.
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March-2020
Volume 21 Issue 3

Print ISSN: 1791-2997
Online ISSN:1791-3004

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APA
Chen, W., Li, Y., Hsu, C., Niu, C., Pen, W., Cheng, K., & Niu, H. (2020). Connective tissue growth factor in hepatocytes is elevated by carbon tetrachloride via STAT3 activation. Molecular Medicine Reports, 21, 1390-1398. https://doi.org/10.3892/mmr.2020.10916
MLA
Chen, W., Li, Y., Hsu, C., Niu, C., Pen, W., Cheng, K., Niu, H."Connective tissue growth factor in hepatocytes is elevated by carbon tetrachloride via STAT3 activation". Molecular Medicine Reports 21.3 (2020): 1390-1398.
Chicago
Chen, W., Li, Y., Hsu, C., Niu, C., Pen, W., Cheng, K., Niu, H."Connective tissue growth factor in hepatocytes is elevated by carbon tetrachloride via STAT3 activation". Molecular Medicine Reports 21, no. 3 (2020): 1390-1398. https://doi.org/10.3892/mmr.2020.10916