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Heme oxygenase‑1 exerts pro‑apoptotic effects on hepatic stellate cells in vitro through regulation of nuclear factor‑κB

  • Authors:
    • Hui Yang
    • Bangtao Chen
    • Zhongfu Zhao
    • Li Zhang
    • Yun Zhang
    • Jie Chen
    • Xiaoqian Zhang
    • Xiaohua Zhang
    • Longfeng Zhao
  • View Affiliations / Copyright

    Affiliations: Department of Infectious Diseases, The First Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China, Department of Microbiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, P.R. China, Institute of Hepatopathy, Changzhi Medical College, Changzhi, Shanxi 046011, P.R. China
    Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 291-299
    |
    Published online on: May 18, 2018
       https://doi.org/10.3892/etm.2018.6185
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Abstract

Heme oxygenase-1 (HO-1) is an antioxidant and cytoprotective protein, which has been proven to alleviate the proliferation of hepatic stellate cells (HSCs) and the development of liver fibrosis. However, the role of HO‑1 in HSC apoptosis remains unclear. The aim of the present study was to investigate the effect of HO‑1 on HSC apoptosis and its possible underlying mechanisms. HSCs‑T6 were incubated with different concentrations of hemin (HO‑1 chemical inducer) and Znpp‑IX (HO‑1 chemical inhibitor) for 12, 24 and 48 h. Cell viability was determined using an MTT assay. HSCs were classified into 4 groups as follows: Control, hemin, Znpp‑IX and hemin+Znpp‑IX co‑treatment groups. Apoptosis was quantitatively measured by Annexin V/propidium iodide double staining and a terminal deoxynucleotidyl transferase dUTP nick‑end labeling assay. The mRNA and protein expression of HO‑1, α‑smooth muscle actin, B‑cell lymphoma (Bcl)‑2, caspase‑3 and nuclear factor (NF)‑κB p65 were measured using quantitative polymerase chain reaction and western blotting. The levels of tumor growth factor (TGF)‑β and interleukin (IL)‑6 in HSC supernatants were examined by ELISA. The results demonstrated that HO‑1 exerted antiproliferative effects on HSCs in a time‑ and concentration‑dependent manner. Increasing HO‑1 expression induced HSC apoptosis in vitro as demonstrated by a significant decrease in Bcl‑2 and an increase in caspase‑3 expression. Additionally, the expression of NF‑κB p65 and its downstream inflammatory factors TGF‑β and IL‑6 in the HO‑1 overexpression group was significantly decreased compared with the control group. Therefore, the present study provided evidence that HO‑1 serves an anti‑fibrosis role in the liver by enhancing HSC apoptosis, which was partially associated with the regulation of NF‑κB and its downstream effectors.
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Copy and paste a formatted citation
Spandidos Publications style
Yang H, Chen B, Zhao Z, Zhang L, Zhang Y, Chen J, Zhang X, Zhang X and Zhao L: Heme oxygenase‑1 exerts pro‑apoptotic effects on hepatic stellate cells in vitro through regulation of nuclear factor‑κB. Exp Ther Med 16: 291-299, 2018.
APA
Yang, H., Chen, B., Zhao, Z., Zhang, L., Zhang, Y., Chen, J. ... Zhao, L. (2018). Heme oxygenase‑1 exerts pro‑apoptotic effects on hepatic stellate cells in vitro through regulation of nuclear factor‑κB. Experimental and Therapeutic Medicine, 16, 291-299. https://doi.org/10.3892/etm.2018.6185
MLA
Yang, H., Chen, B., Zhao, Z., Zhang, L., Zhang, Y., Chen, J., Zhang, X., Zhang, X., Zhao, L."Heme oxygenase‑1 exerts pro‑apoptotic effects on hepatic stellate cells in vitro through regulation of nuclear factor‑κB". Experimental and Therapeutic Medicine 16.1 (2018): 291-299.
Chicago
Yang, H., Chen, B., Zhao, Z., Zhang, L., Zhang, Y., Chen, J., Zhang, X., Zhang, X., Zhao, L."Heme oxygenase‑1 exerts pro‑apoptotic effects on hepatic stellate cells in vitro through regulation of nuclear factor‑κB". Experimental and Therapeutic Medicine 16, no. 1 (2018): 291-299. https://doi.org/10.3892/etm.2018.6185
Copy and paste a formatted citation
x
Spandidos Publications style
Yang H, Chen B, Zhao Z, Zhang L, Zhang Y, Chen J, Zhang X, Zhang X and Zhao L: Heme oxygenase‑1 exerts pro‑apoptotic effects on hepatic stellate cells in vitro through regulation of nuclear factor‑κB. Exp Ther Med 16: 291-299, 2018.
APA
Yang, H., Chen, B., Zhao, Z., Zhang, L., Zhang, Y., Chen, J. ... Zhao, L. (2018). Heme oxygenase‑1 exerts pro‑apoptotic effects on hepatic stellate cells in vitro through regulation of nuclear factor‑κB. Experimental and Therapeutic Medicine, 16, 291-299. https://doi.org/10.3892/etm.2018.6185
MLA
Yang, H., Chen, B., Zhao, Z., Zhang, L., Zhang, Y., Chen, J., Zhang, X., Zhang, X., Zhao, L."Heme oxygenase‑1 exerts pro‑apoptotic effects on hepatic stellate cells in vitro through regulation of nuclear factor‑κB". Experimental and Therapeutic Medicine 16.1 (2018): 291-299.
Chicago
Yang, H., Chen, B., Zhao, Z., Zhang, L., Zhang, Y., Chen, J., Zhang, X., Zhang, X., Zhao, L."Heme oxygenase‑1 exerts pro‑apoptotic effects on hepatic stellate cells in vitro through regulation of nuclear factor‑κB". Experimental and Therapeutic Medicine 16, no. 1 (2018): 291-299. https://doi.org/10.3892/etm.2018.6185
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