Abstract
Abstract
Background
Liver fibrosis is a progressive liver injury response. Transforming growth factor β1 (TGF-β1) is oversecreted during liver fibrosis and promotes the development of liver fibrosis. Therapeutic approaches targeting TGF-β1 and its downstream pathways are essential to inhibit liver fibrosis. The N-terminal latency-associated peptide (LAP) blocks the binding of TGF-β1 to its receptor. Removal of LAP is critical for the activation of TGF-β1. Therefore, inhibition of TGF-β1 and its downstream pathways by LAP may be a potential approach to affect liver fibrosis.
Methods
Truncated LAP (tLAP) plasmids were constructed. Recombinant proteins were purified by Ni affinity chromatography. The effects of LAP and tLAP on liver fibrosis were investigated in TGF-β1-induced HSC-T6 cells, AML12 cells and CCl4-induced liver fibrosis mice by real time cellular analysis (RTCA), western blot, real-time quantitative PCR (RT-qPCR), immunofluorescence and pathological staining.
Results
LAP and tLAP could inhibit TGF-β1-induced AML12 cells inflammation, apoptosis and EMT, and could inhibit TGF-β1-induced HSC-T6 cells proliferation and fibrosis. LAP and tLAP could attenuate the pathological changes of liver fibrosis and inhibit the expression of fibrosis-related proteins and mRNAs in CCl4-induced liver fibrosis mice.
Conclusion
LAP and tLAP could alleviate liver fibrosis in vitro and in vivo via inhibition of TGF-β/Smad pathway. TLAP has higher expression level and more effective anti-fibrosis activity compared to LAP. This study may provide new ideas for the treatment of liver fibrosis.
Funder
Central Finance supports Local Colleges, and Universities Talent Development Funding from Heilongjiang Provincial Department of Finance
Natural Science Foundation of Heilongjiang Province
the Basic Scientific Research Project of University belongs to Heilongjiang
National Natural Science Foundation of China
Publisher
Springer Science and Business Media LLC
Subject
Genetics (clinical),Genetics,Molecular Biology,Molecular Medicine
Cited by
5 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献