Adenovirus‑mediated overexpression of bone morphogenetic protein‑9 promotes methionine choline deficiency‑induced non‑alcoholic steatohepatitis in non‑obese mice

Li,Qi; Liu,Beibei; Breitkopf‑Heinlein,Katja; Weng,Honglei; Jiang,Qianqian; Dong,Peiling; Dooley,Steven; Xu,Keshu; Ding,Huiguo

doi:10.3892/mmr.2019.10508

Adenovirus‑mediated overexpression of bone morphogenetic protein‑9 promotes methionine choline deficiency‑induced non‑alcoholic steatohepatitis in non‑obese mice

Authors:
- Qi Li
- Beibei Liu
- Katja Breitkopf‑Heinlein
- Honglei Weng
- Qianqian Jiang
- Peiling Dong
- Steven Dooley
- Keshu Xu
- Huiguo Ding
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Affiliations: Department of Hepatology and Gastroenterology, Beijing You An Hospital, Capital Medical University, Beijing 100069, P.R. China, Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China, Department of Medicine II, Medical Faculty Mannheim, Heidelberg University, D‑68167 Mannheim, Germany
Published online on: July 19, 2019 https://doi.org/10.3892/mmr.2019.10508
Pages: 2743-2753
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Liver inflammation and macrophage infiltration are critical steps in the progression of non‑alcoholic fatty liver to the development of non‑alcoholic steatohepatitis. Bone morphogenetic protein‑9 is a cytokine involved in the regulation of chemokines and lipogenesis. However, the function of bone morphogenetic protein‑9 in non‑alcoholic steatohepatitis is still unknown. The present study hypothesized that bone morphogenetic protein‑9 may contribute to steatohepatitis in mice fed a methionine choline deficiency diet (MCD). C57BL/6 mice overexpressing bone morphogenetic protein‑9 and control mice were fed the MCD diet for 4 weeks. Liver tissue and serum samples were obtained for subsequent measurements. Bone morphogenetic protein‑9 overexpression exacerbated steatohepatitis in mice on the MCD diet, as indicated by liver histopathology, increased serum alanine aminotransferase activity, aspartate transaminase activity, hepatic inflammatory gene expression and M1 macrophage recruitment. Although bone morphogenetic protein‑9 overexpression did not affect the expression of pro‑fibrogenic genes, including Collagen I (α)1 or matrix metalloproteinase (MMP) 9, it did upregulate the expression of transforming growth factor‑β and plasminogen activator inhibitor 1, and downregulated the expression of MMP2. The above results indicate that bone morphogenetic protein‑9 exerts a pro‑inflammatory role in MCD diet‑induced non‑alcoholic steatohepatitis.

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