Downregulation of Glt25d1 aggravates carbon tetrachloride‑induced acute hepatic injury through activation of the TGF‑β1/Smad2 signaling pathway

Ye,Xiaohui; He,Lingling; Ma,Jiali; Li,Yufeng; Zhang,Manka; Yang,Junru; Zhang,Jian; Xiao,Fan; Wei,Hongshan

doi:10.3892/mmr.2018.9392

Downregulation of Glt25d1 aggravates carbon tetrachloride‑induced acute hepatic injury through activation of the TGF‑β1/Smad2 signaling pathway

Authors:
- Xiaohui Ye
- Lingling He
- Jiali Ma
- Yufeng Li
- Manka Zhang
- Junru Yang
- Jian Zhang
- Fan Xiao
- Hongshan Wei
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Affiliations: Department of Gastroenterology, Peking University Ditan Teaching Hospital, Beijing 100015, P.R. China , Department of Gastroenterology, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, P.R. China, Department of Gastroenterology, Beijing Changping Hospital, Beijing 100085, P.R. China, Department of Center of Integrated Traditional Chinese and Western Medicine, Peking University Ditan Teaching Hospital, Beijing 100015, P.R. China, Department of Institute of Infectious Disease, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, P.R. China
Published online on: August 16, 2018 https://doi.org/10.3892/mmr.2018.9392
Pages: 3611-3618
Copyright: © Ye et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Collagen β (1‑O) galactosyltransferase 1 (GLT25D1) has been reported to transfer galactose to hydroxylysine residues via β (1‑O) linkages in collagen. The present study investigated the function of the collagen galactosyltransferase activity of GLT25D1 against carbon tetrachloride (CCl4)‑induced acute liver injury in vitro. Glt25d1+/‑ mice and wild‑type (WT) mice were injected intraperitoneally with the same dose of CCl4. The grade of hepatic injury and the extent of hepatocyte necrosis in the acute phase were assessed 48 h following CCl4 injection. Hepatocyte necrosis was evaluated by histological examination and by serum alanine aminotransferase and aspartate aminotransferase levels, which were higher in the Glt25d1+/‑ mice compared with those in the WT mice. Reverse transcription‑quantitative polymerase chain reaction was performed, and the results demonstrated that the mRNA expression levels of inflammatory cytokines, including tumor necrosis factor‑α and interleukin‑6 were significantly increased in the Glt25d1+/‑ mice. Furthermore, western blot analyses were performed, and the results demonstrated that the protein levels of cleaved caspase‑3 and ‑9 were also markedly increased in the Glt25d1+/‑ liver, indicating that hepatocyte apoptosis was induced. Additionally, the expression levels of transforming growth factor (TGF)‑β1 and phosphorylated small mothers against decapentaplegic (Smad)2 were markedly upregulated, indicating activation of the TGF‑β1/Smad2 signaling pathway during CCl4‑induced acute liver injury in Glt25d1+/‑ mice. CCl4 administration also resulted in severe damage to Glt25d1+/‑ primary hepatocytes in vitro. Taken together, the downregulation of Glt25d1 deteriorated CCl4‑induced liver injury in mice, which may involve triggering inflammatory responses, apoptosis and TGF‑β1/Smad2 signaling pathway activation.

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