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Activation of nuclear factor kappa B (NF-κB) by connective tissue growth factor (CCN2) is involved in sustaining the survival of primary rat hepatic stellate cells

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dc.creator Gao, Runping
dc.creator Brigstock, David R.
dc.date.accessioned 2011-02-15T18:57:19Z
dc.date.available 2011-02-15T18:57:19Z
dc.date.issued 2005-11-22
dc.identifier.citation Runping Gao and David R. Brigstock, "Activation of nuclear factor kappa B (NF-κB) by connective tissue growth factor (CCN2) is involved in sustaining the survival of primary rat hepatic stellate cells," Cell Communication and Signaling 3 (2005), doi:10.1186/1478-811X-3-14, http://www.biosignaling.com/content/3/1/14 en_US
dc.identifier.issn 1478-811X
dc.identifier.uri http://hdl.handle.net/1811/47938
dc.description.abstract Background/Aims: Connective tissue growth factor (CCN2) is a matricellular protein that plays a role in hepatic stellate cell (HSC)-mediated fibrogenesis. The aim of this study was to investigate the regulation by CCN2 of cell survival pathways in primary HSC. Methods: Primary HSC were obtained by in situ enzymatic perfusion of rat liver. NF-κB activation was assessed by immunoblotting for IκBα phosphorylation and degradation and by NF-κB p50 or p65 nuclear accumulation. NF-κB DNA-binding activity was determined by gel mobility shift assay while NF-κB response gene expression was evaluated using a luciferase reporter. Cell viability was assessed by Trypan blue staining or ATP luminescent assay while apoptosis was evaluated by caspase-3 activity. Results: CCN2 induced IκBα phosphorylation and degradation as well as nuclear accumulation of NF-κB. Activated NF-κB comprised three dimers, p65/p65, p65/p50 and p50/p50, that individually bound to DNA-binding sites and subsequently triggered transcriptional activity. This was confirmed by showing that CCN2 promoted activity of a NF-κB luciferase reporter. CCN2 promoted survival of serum-starved HSC and protected the cells from death induced by blocking the NF-κB signaling pathway using Bay-11-7082, a specific inhibitor of IκBα phosphorylation. Conclusion: CCN2 contributes to the survival of primary HSC through the NF-κB pathway. en_US
dc.language.iso en_US en_US
dc.publisher BioMed Central en_US
dc.title Activation of nuclear factor kappa B (NF-κB) by connective tissue growth factor (CCN2) is involved in sustaining the survival of primary rat hepatic stellate cells en_US
dc.type Article en_US
dc.identifier.doi 10.1186/1478-811X-3-14
dc.identifier.osuauthor brigstock.1
dc.rights.cc Attribution 3.0 Unported en_US
dc.rights.ccuri http://creativecommons.org/licenses/by/3.0/ en_US
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