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Aggravation of hepatic ischemia‑reperfusion injury with increased inflammatory cell infiltration is associated with the TGF‑β/Smad3 signaling pathway

  • Authors:
    • Haixia Li
    • Xiaoyun Shen
    • Yifan Tong
    • Tong Ji
    • Yan Feng
    • Yanping Tang
    • Rongyun Mai
    • Jiaxiang Ye
    • Ting Que
    • Xiaoling Luo

  • View Affiliations

  • Published online on: June 14, 2021     https://doi.org/10.3892/mmr.2021.12219
  • Article Number: 580

  • Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Ischemia‑reperfusion (IR) injury is a major challenge influencing the outcomes of hepatic transplantation. Transforming growth factor‑β (TGF‑β) and its downstream gene, SMAD family member 3 (Smad3), have been implicated in the pathogenesis of chronic hepatic injuries, such as hepatic fibrosis. Thus, the present study aimed to investigate the role of the TGF‑β/Smad3 signaling pathway on hepatic injury induced by IR in vivo. In total, 20 129S2/SvPasCrl wild‑type (WT) mice were randomized into two groups; 10 mice underwent IR injury surgery and 10 mice were sham‑operated. Histopathological changes in liver tissues and serum levels of alanine aminotransferase (ALT) were examined to confirm hepatic injury caused by IR surgery. The expression levels of TGF‑β1, Smad3 and phosphorylated‑Smad3 (p‑Smad3) were detected via western blotting. Furthermore, a total of five Smad3‑/‑ 129S2/SvPasCrl mice (Smad3‑/‑ mice) and 10 Smad3+/+ littermates received IR surgery, while another five Smad3‑/‑ mice and 10 Smad3+/+ littermates received the sham operation. Histopathological changes in liver tissues and serum levels of ALT were then compared between the groups. Furthermore, hepatic apoptosis and inflammatory cell infiltration after IR were evaluated in the liver tissues of Smad3‑/‑ mice and Smad3+/+ mice. The results demonstrated that the expression levels of TGF‑β1, Smad3 and p‑Smad3 were elevated in hepatic tissue from WT mice after IR injury. Aggravated hepatic injury, increased apoptosis and enhanced inflammatory cell infiltration induced by hepatic IR injury were observed in the Smad3‑/‑ mice compared with in Smad3+/+ mice. Collectively, the current findings suggested that activation of the TGF‑β/Smad3 signaling pathway was present alongside the hepatic injury induced by IR. However, the TGF‑β/Smad3 signaling pathway may have an effect on protecting against liver tissue damage caused by IR injury in vivo.
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August-2021
Volume 24 Issue 2

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

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Spandidos Publications style
Li H, Shen X, Tong Y, Ji T, Feng Y, Tang Y, Mai R, Ye J, Que T, Luo X, Luo X, et al: Aggravation of hepatic ischemia‑reperfusion injury with increased inflammatory cell infiltration is associated with the TGF‑β/Smad3 signaling pathway. Mol Med Rep 24: 580, 2021.
APA
Li, H., Shen, X., Tong, Y., Ji, T., Feng, Y., Tang, Y. ... Luo, X. (2021). Aggravation of hepatic ischemia‑reperfusion injury with increased inflammatory cell infiltration is associated with the TGF‑β/Smad3 signaling pathway. Molecular Medicine Reports, 24, 580. https://doi.org/10.3892/mmr.2021.12219
MLA
Li, H., Shen, X., Tong, Y., Ji, T., Feng, Y., Tang, Y., Mai, R., Ye, J., Que, T., Luo, X."Aggravation of hepatic ischemia‑reperfusion injury with increased inflammatory cell infiltration is associated with the TGF‑β/Smad3 signaling pathway". Molecular Medicine Reports 24.2 (2021): 580.
Chicago
Li, H., Shen, X., Tong, Y., Ji, T., Feng, Y., Tang, Y., Mai, R., Ye, J., Que, T., Luo, X."Aggravation of hepatic ischemia‑reperfusion injury with increased inflammatory cell infiltration is associated with the TGF‑β/Smad3 signaling pathway". Molecular Medicine Reports 24, no. 2 (2021): 580. https://doi.org/10.3892/mmr.2021.12219