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

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Abstract

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.

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

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Publication details

The article was received on 28 Aug 2019, accepted on 31 Oct 2019 and first published on 02 Nov 2019


Article type: Paper
DOI: 10.1039/C9TB01845J
J. Mater. Chem. B, 2019, Advance Article

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

    J. L. Vivero-Escoto, H. Vadarevu, R. Juneja, L. W. Schrum and J. H. Benbow, J. Mater. Chem. B, 2019, Advance Article , DOI: 10.1039/C9TB01845J

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