Nanoparticle mediated silencing of tenascin C in hepatic stellate cells: effect on inflammatory gene expression and cell migration

Autor: Juan L. Vivero-Escoto, Hemapriyadarshini Vadarevu, Laura W. Schrum, Jennifer H Benbow, Ridhima Juneja
Rok vydání: 2019
Předmět:
Liver Cirrhosis
Male
Liver cytology
02 engineering and technology
01 natural sciences
Rats
Sprague-Dawley
Mice
Fibrosis
Cell Movement
General Materials Science
RNA
Small Interfering
Extracellular Matrix Proteins
biology
Chemistry
Tenascin C
Cell migration
Tenascin
General Medicine
musculoskeletal system
021001 nanoscience & nanotechnology
Silicon Dioxide
Extracellular Matrix
medicine.anatomical_structure
Nanomedicine
Liver
Hepatocyte
Disease Progression
0210 nano-technology
Cell Survival
Biomedical Engineering
010402 general chemistry
medicine
Hepatic Stellate Cells
Gene silencing
Animals
Humans
Gene Silencing
Inflammation
General Chemistry
medicine.disease
0104 chemical sciences
Rats
Mice
Inbred C57BL
Gene Expression Regulation
Cancer research
biology.protein
Hepatic stellate cell
Hepatocytes
Nanoparticles
Hepatic fibrosis
Zdroj: Journal of materials chemistry. B. 7(46)
ISSN: 2050-7518
Popis: Chronic liver dysfunction often begins with hepatic fibrosis. A pivotal event in the progression of liver fibrosis and cirrhosis is hepatic stellate cell (HSC) activation and secretion of extracellular matrix proteins, including tenascin-C (TnC). TnC is often chosen as a therapeutic target for treatment of liver disease. TnC is minimally detected in healthy tissue, but is transiently expressed during tissue injury, and plays a critical role in fibrogenesis and tumorigenesis. siRNA therapy is a promising alternative to knock-down proteins relevant for fibrosis therapy. This study describes the application of a functionalized mesoporous silica nanoparticles (MSNs) for the efficient transport and delivery of siTnC in HSCs. Silencing experiments in HSCs demonstrate the effective reduction of TnC mRNA and protein levels. In addition, attenuation of TnC expression due to the cellular uptake and release of siTnC from MSNs resulted in decreases of inflammatory cytokine levels and hepatocyte migration. We envision this siTnC-MSN platform as a promising alternative to evaluate siRNA therapy of chronic liver disease in preclinical trials.
Databáze: OpenAIRE
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