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

Content Provider	PubMed Central
Author	Liu, Jinghua Li, Jianbo Weiwei, Fu Tang, Jiacheng Feng, Xu Chen, Jiang Liang, Yuelong Jin, Renâ an Xie, Anyong Cai, Xiujun
Copyright Year	2015
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 metal-loproteinase 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.
Related Links	http://dx.doi.org/10.2147/dddt.s92481
Ending Page	5667
Page Count	13
Starting Page	5655
File Format	PDF
ISSN	11778881
e-ISSN	11778881
Journal	Drug Design, Development and Therapy
Volume Number	9
Language	English
Publisher	Dove Medical Press
Publisher Date	2015-10-01
Access Restriction	Open
Rights Holder	Dove Medical Press
Subject Keyword	Pharmacology Drug Discovery Pharmaceutical Science Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Drug Discovery Pharmacology Pharmaceutical Science

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