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Adenoviral delivery of truncated MMP-8 fused with the hepatocyte growth factor mutant 1K1 ameliorates liver cirrhosis and promotes hepatocyte proliferation

Authors Liu J, Li J, Fu W, Tang J, Feng X, Chen J, Liang Y, Jin R, Xie A, Cai X, Meng F

Received 16 July 2015

Accepted for publication 19 August 2015

Published 16 October 2015 Volume 2015:9 Pages 5655—5667

DOI https://doi.org/10.2147/DDDT.S92481

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Prof. Dr. Wei Duan


Jinghua Liu,1 Jianbo Li,1 Weiwei Fu,2 Jiacheng Tang,3 Xu Feng,1 Jiang Chen,1 Yuelong Liang,1 Ren’an Jin,1 Anyong Xie,4 Xiujun Cai1,3

1Department of General Surgery, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang, 2Department of Pathology, The Affiliated Hospital of Medical College, Qingdao University, Qingdao, Shandong, 3Key Lab of Surgery of Zhejiang Province, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang, 4Sir Run Run Shaw Hospital and Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China

Abstract: Liver cirrhosis is a chronic liver disease caused by chronic liver injury, which activates hepatic stellate cells (HSCs) and the secretion of extracellular matrix (ECM). Cirrhosis accounts for an extensive level of morbidity and mortality worldwide, largely due to lack of effective treatment options. In this study, we have constructed a fusion protein containing matrix metalloproteinase 8 (MMP-8) and the human growth factor mutant 1K1 (designated cMMP8-1K1) and delivered it into hepatocytes and in vivo and in cell culture via intravenous injection of fusion protein-harboring adenovirus. In doing so, we found that the cMMP8-1K1 fusion protein promotes the proliferation of hepatocytes, likely resulting from the combined inhibition of type I collagen secretion and the degradation of the ECM in the HSCs. This fusion protein was also observed to ameliorate liver cirrhosis in our mouse model. These changes appear to be linked to changes in downstream gene expression. Taken together, these results suggest a possible strategy for the treatment of liver cirrhosis and additional work is warranted.

Keywords: liver cirrhosis, MMP-8, HGF, hepatocytes proliferation

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