期刊
HEPATOLOGY
卷 62, 期 4, 页码 1285-1297出版社
WILEY
DOI: 10.1002/hep.27936
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资金
- Graduate Center for Immunology, Johannes Guttenberg University [GRK1043]
- National Institutes of Health [U19 AI066313]
- German Research Foundation
- Ministry for Research and Education of the State of Rhineland-Palatinate, Germany
Fibrosis accompanies the wound-healing response to chronic liver injury and is characterized by excessive hepatic collagen accumulation dominated by collagen type I. Fibrosis often progresses to cirrhosis. Here we present in vivo evidence of an up to 90% suppression of procollagen 1(I) expression, a reduction of septa formation, and a 40%-60% decrease of collagen deposition in mice with progressive and advanced liver fibrosis that received cationic lipid nanoparticles loaded with small interfering RNA to the procollagen 1(I) gene. After intravenous injection, up to 90% of lipid nanoparticles loaded with small interfering RNA to the procollagen 1(I) gene were retained in the liver of fibrotic mice and accumulated in nonparenchymal more than parenchymal cells for prolonged periods, significantly ameliorating progression and accelerating regression of fibrosis. Conclusion: Our lipid nanoparticles loaded with small interfering RNA to the procollagen 1(I) gene specifically reduce total hepatic collagen content without detectable side effects, potentially qualifying as a therapy for fibrotic liver diseases. (Hepatology 2015;62:1285-1297)
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