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Article Open Access

Heme oxygenase‑1 inhibits renal tubular epithelial cell pyroptosis by regulating mitochondrial function through PINK1

  • Authors:
    • Hai-Bo Li
    • Yan-Shuai Mo
    • Xi-Zhe Zhang
    • Qi Zhou
    • Xiao-Dong Liang
    • Jian-Nan Song
    • Li-Na Hou
    • Jian-Nan Wu
    • Ying Guo
    • Dan-Dan Feng
    • Yi Sun
    • Jian-Bo Yu
  • View Affiliations / Copyright

    Affiliations: Department of Anesthesiology, Chifeng Municipal Hospital, Chifeng, Inner Mongolia 024000, P.R. China, Department of Anesthesiology and Critical Care Medicine, Tianjin Nankai Hospital, Tianjin Medical University, Tianjin 300102, P.R. China
    Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 213
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    Published online on: March 24, 2023
       https://doi.org/10.3892/etm.2023.11912
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Abstract

Endotoxin‑induced acute kidney injury (AKI) is commonly observed in clinical practice. Renal tubular epithelial cell (RTEC) pyroptosis is one of the main factors leading to the development of endotoxin‑induced AKI. Mitochondrial dysfunction can lead to pyroptosis. However, the biological pathways involved in the potential lipopolysaccharide (LPS)‑induced pyroptosis of RTECs, notably those associated with mitochondrial dysfunction, are poorly understood. Previous studies have demonstrated that heme oxygenase (HO)‑1 confers cell protection via the induction of PTEN‑induced putative kinase 1 (PINK1) expression through PTEN to regulate mitochondrial fusion/fission during endotoxin‑induced AKI in vivo. Therefore, the present study investigated the role of HO‑1/PINK1 in maintaining mitochondrial function and inhibiting the pyroptosis of RTECs exposed to LPS. Primary cultures of RTECs were obtained from wild‑type (WT) and PINK1‑knockout (PINK1KO) rats. An in vitro model of endotoxin‑associated RTEC injury was established following treatment of the cells with LPS. The WT RTECs were divided into the control, LPS, Znpp + LPS and Hemin + LPS groups, and the PINK1KO RTECs were divided into the control, LPS and Hemin + LPS groups. RTECs were exposed to LPS for 6 h to assess cell viability, inflammation, pyroptosis and mitochondrial function. In the LPS‑treated RTECs, the mRNA and protein expression levels of HO‑1 and PINK1 were upregulated. Cell viability, adenosine triphosphate (ATP) levels and the mitochondrial oxygen consumption rate were decreased, whereas the inflammatory response, pyroptosis and mitochondrial reactive oxygen species (ROS) levels were increased. The cell inflammatory response and the induction of pyroptosis were inhibited, whereas the levels of mitochondrial ROS were decreased. In addition, the cell viability and ATP levels were increased in the WT RTECs following the upregulation of HO‑1 expression. These effects were reversed by the downregulation of HO‑1 expression. However, no statistically significant differences were noted between the LPS and the Hemin + LPS groups in the PINK1KO RTECs. Collectively, the findings of the present study indicate that HO‑1 inhibits inflammation and regulates mitochondrial function by inhibiting the pyroptosis of LPS‑exposed RTECs via PINK1.
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Copy and paste a formatted citation
Spandidos Publications style
Li H, Mo Y, Zhang X, Zhou Q, Liang X, Song J, Hou L, Wu J, Guo Y, Feng D, Feng D, et al: Heme oxygenase‑1 inhibits renal tubular epithelial cell pyroptosis by regulating mitochondrial function through PINK1. Exp Ther Med 25: 213, 2023.
APA
Li, H., Mo, Y., Zhang, X., Zhou, Q., Liang, X., Song, J. ... Yu, J. (2023). Heme oxygenase‑1 inhibits renal tubular epithelial cell pyroptosis by regulating mitochondrial function through PINK1. Experimental and Therapeutic Medicine, 25, 213. https://doi.org/10.3892/etm.2023.11912
MLA
Li, H., Mo, Y., Zhang, X., Zhou, Q., Liang, X., Song, J., Hou, L., Wu, J., Guo, Y., Feng, D., Sun, Y., Yu, J."Heme oxygenase‑1 inhibits renal tubular epithelial cell pyroptosis by regulating mitochondrial function through PINK1". Experimental and Therapeutic Medicine 25.5 (2023): 213.
Chicago
Li, H., Mo, Y., Zhang, X., Zhou, Q., Liang, X., Song, J., Hou, L., Wu, J., Guo, Y., Feng, D., Sun, Y., Yu, J."Heme oxygenase‑1 inhibits renal tubular epithelial cell pyroptosis by regulating mitochondrial function through PINK1". Experimental and Therapeutic Medicine 25, no. 5 (2023): 213. https://doi.org/10.3892/etm.2023.11912
Copy and paste a formatted citation
x
Spandidos Publications style
Li H, Mo Y, Zhang X, Zhou Q, Liang X, Song J, Hou L, Wu J, Guo Y, Feng D, Feng D, et al: Heme oxygenase‑1 inhibits renal tubular epithelial cell pyroptosis by regulating mitochondrial function through PINK1. Exp Ther Med 25: 213, 2023.
APA
Li, H., Mo, Y., Zhang, X., Zhou, Q., Liang, X., Song, J. ... Yu, J. (2023). Heme oxygenase‑1 inhibits renal tubular epithelial cell pyroptosis by regulating mitochondrial function through PINK1. Experimental and Therapeutic Medicine, 25, 213. https://doi.org/10.3892/etm.2023.11912
MLA
Li, H., Mo, Y., Zhang, X., Zhou, Q., Liang, X., Song, J., Hou, L., Wu, J., Guo, Y., Feng, D., Sun, Y., Yu, J."Heme oxygenase‑1 inhibits renal tubular epithelial cell pyroptosis by regulating mitochondrial function through PINK1". Experimental and Therapeutic Medicine 25.5 (2023): 213.
Chicago
Li, H., Mo, Y., Zhang, X., Zhou, Q., Liang, X., Song, J., Hou, L., Wu, J., Guo, Y., Feng, D., Sun, Y., Yu, J."Heme oxygenase‑1 inhibits renal tubular epithelial cell pyroptosis by regulating mitochondrial function through PINK1". Experimental and Therapeutic Medicine 25, no. 5 (2023): 213. https://doi.org/10.3892/etm.2023.11912
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