%0 Journal Article
%T Activation of nuclear factor kappa B (NF-百B) by connective tissue growth factor (CCN2) is involved in sustaining the survival of primary rat hepatic stellate cells
%A Runping Gao
%A David R Brigstock
%J Cell Communication and Signaling
%D 2005
%I BioMed Central
%R 10.1186/1478-811x-3-14
%X Primary HSC were obtained by in situ enzymatic perfusion of rat liver. NF-百B activation was assessed by immunoblotting for I百B汐 phosphorylation and degradation and by NF-百B p50 or p65 nuclear accumulation. NF-百B DNA-binding activity was determined by gel mobility shift assay while NF-百B 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.CCN2 induced I百B汐 phosphorylation and degradation as well as nuclear accumulation of NF-百B. Activated NF-百B 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-百B luciferase reporter. CCN2 promoted survival of serum-starved HSC and protected the cells from death induced by blocking the NF-百B signaling pathway using Bay-11-7082, a specific inhibitor of I百B汐 phosphorylation.CCN2 contributes to the survival of primary HSC through the NF-百B pathway.Hepatic stellate cells (HSC) are the primary targets of fibrogenic stimuli in the injured liver. During the development of fibrosis, HSC undergo a transition from resting vitamin A-rich cells to an activated myofibroblastic phenotype characterized by loss of vitamin A, expression of 汐-smooth muscle actin, enhanced proliferation and increased production of various extracellular matrix components [1-4]. Activation of HSC has been identified as a central event in hepatic fibrosis and is regulated by a wide variety of molecules including cytokines, cell-surface receptors, signal transduction molecules and factors that regulate HSC gene expression at the transcriptional and post-transcriptional levels [3-6].Connective tissue growth factor (CCN2, also known as CTGF) is a cysteine-rich matricellular protein that regulates cell adhesion, migration, proliferation, survival, and differentiation [7
%K connective tissue growth factor
%K CCN2
%K hepatic stellate cell
%K NF-百B
%K survival
%K apoptosis
%K fibrosis
%U http://www.biosignaling.com/content/3/1/14