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Aggravation of hepatic ischemia-reperfusion injury with increased inflammatory cell infiltration is associated with the TGF-β/Smad3 signaling pathway
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,...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8223105/ https://www.ncbi.nlm.nih.gov/pubmed/34132369 http://dx.doi.org/10.3892/mmr.2021.12219 |
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author | Li, Haixia Shen, Xiaoyun Tong, Yifan Ji, Tong Feng, Yan Tang, Yanping Mai, Rongyun Ye, Jiaxiang Que, Ting Luo, Xiaoling |
author_facet | Li, Haixia Shen, Xiaoyun Tong, Yifan Ji, Tong Feng, Yan Tang, Yanping Mai, Rongyun Ye, Jiaxiang Que, Ting Luo, Xiaoling |
author_sort | Li, Haixia |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8223105 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-82231052021-06-26 Aggravation of hepatic ischemia-reperfusion injury with increased inflammatory cell infiltration is associated with the TGF-β/Smad3 signaling pathway Li, Haixia Shen, Xiaoyun Tong, Yifan Ji, Tong Feng, Yan Tang, Yanping Mai, Rongyun Ye, Jiaxiang Que, Ting Luo, Xiaoling Mol Med Rep Articles 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. D.A. Spandidos 2021-08 2021-06-14 /pmc/articles/PMC8223105/ /pubmed/34132369 http://dx.doi.org/10.3892/mmr.2021.12219 Text en Copyright: © Li et al. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
spellingShingle | Articles Li, Haixia Shen, Xiaoyun Tong, Yifan Ji, Tong Feng, Yan Tang, Yanping Mai, Rongyun Ye, Jiaxiang Que, Ting Luo, Xiaoling Aggravation of hepatic ischemia-reperfusion injury with increased inflammatory cell infiltration is associated with the TGF-β/Smad3 signaling pathway |
title | Aggravation of hepatic ischemia-reperfusion injury with increased inflammatory cell infiltration is associated with the TGF-β/Smad3 signaling pathway |
title_full | Aggravation of hepatic ischemia-reperfusion injury with increased inflammatory cell infiltration is associated with the TGF-β/Smad3 signaling pathway |
title_fullStr | Aggravation of hepatic ischemia-reperfusion injury with increased inflammatory cell infiltration is associated with the TGF-β/Smad3 signaling pathway |
title_full_unstemmed | Aggravation of hepatic ischemia-reperfusion injury with increased inflammatory cell infiltration is associated with the TGF-β/Smad3 signaling pathway |
title_short | Aggravation of hepatic ischemia-reperfusion injury with increased inflammatory cell infiltration is associated with the TGF-β/Smad3 signaling pathway |
title_sort | aggravation of hepatic ischemia-reperfusion injury with increased inflammatory cell infiltration is associated with the tgf-β/smad3 signaling pathway |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8223105/ https://www.ncbi.nlm.nih.gov/pubmed/34132369 http://dx.doi.org/10.3892/mmr.2021.12219 |
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