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/p5O and p50/p50, that individually bound to DNA-binding sites and subsequently triggered traRscriptional 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 blocldng the NF-κB signaling pathway using Bay-II-7082, a specific inhibitor of IκBα phosphorylation. Conclusion: CCN2 contributes to the survival of primary HSC through the NF-κB pathway. © 2005 Gao and Brigstock; licensee BioMed Central Ltd.
CITATION STYLE
Gao, R., & Brigstock, D. R. (2005). Activation on 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. https://doi.org/10.1186/1478-811X-3-14
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