UV Irradiation Activates JNK and Increases αI(I) Collagen Gene Expression in Rat Hepatic Stellate Cells

Chen, Anping; Davis, Bernard H.

doi:10.1074/jbc.274.1.158

Cited by 77 publications

(82 citation statements)

References 33 publications

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“…Platelet-derived growth factor (PDGF) is known to have most potent activity among these proliferative factors in hepatic fibrosis. This step is associated with both increased autocrine PDGF and up-regulation of PDGF receptor (Chen et al, 1999). Activated PDGF receptor recruits the signaling molecule Ras, followed by activation of the ERK/mitogen-activated protein kinase pathway.…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, activation of phosphoinositol 3-kinase is necessary for both mitogenesis and chemotaxis (Marra et al, 1997). The proliferative response to PDGF also requires a sustained intake of extracellular (Ca 2+ ) and increased intracellular pH (Chen and Davis, 1999). In human HSCs, activation of the ERK pathway followed by an increased expression of c-fos in response to PDGF (Marra et al, 1995;.…”

Section: Discussionmentioning

confidence: 99%

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Cell cycle protein profile of the hepatic stellate cells (HSCs) in dimethylnitrosamine-induced rat hepatic fibrosis

Kim

Kim²,

Lee³

et al. 2005

Exp Mol Med

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Cell cycle protein profile of the hepatic stellate cells (HSCs) in dimethylnitrosamine-induced rat hepatic fibrosis

Kim

Kim²,

Lee³

et al. 2005

Exp Mol Med

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“…For example, serumstimulated ␣1(I) collagen gene expression via extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase/ stress-activated protein kinase (JNK/SAPK) pathways through different regions of the 5Ј-upstream promoter sequence of the gene (26). Although the ERK-stimulatory signal was mapped to the most proximal nuclear factor-1and Sp-1 binding domains, a distal GC box located at Ϫ1484 to Ϫ1476 base pairs played a central role in receiving extracellular signals through the JNK/ SAPK pathway (26). JNK/SAPK and AP-1 activation were also required for the UV-and acetaldehyde-induced increase in FIG.…”

Section: Discussionmentioning

confidence: 99%

Ligands of Peroxisome Proliferator-activated Receptor-γ Block Activation of Pancreatic Stellate Cells

Masamune

Kikuta

Satoh

et al. 2002

Journal of Biological Chemistry

133

112

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“…On the other hand, fibrogenic effects induced by the activation of MAPK pathways have been shown for a variety of different other stimuli that converge at the level of transcription of fibrogenic genes. 36,43 Thus, direct activation of fibrogenesis by HCV core protein may have considerable pathophysiological relevance.…”

Section: Hcv Core Protein Induces Fibrogenesis M Coenen Et Almentioning

confidence: 99%

Hepatitis C virus core protein induces fibrogenic actions of hepatic stellate cells via toll-like receptor 2

Coenen

Nischalke

Krämer

et al. 2011

Laboratory Investigation

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Hepatic stellate cells (HSCs) represent the main fibrogenic cell type accumulating extracellular matrix in the liver. Recent data suggest that hepatitis C virus (HCV) core protein may directly activate HSCs. Therefore, we examined the influence of recombinant HCV core protein on human HSCs. Primary human HSCs and the human HSC line LX-2 were stimulated with recombinant HCV proteins core and envelope 2 protein. Expression of procollagen type I a-1, a-smooth muscle actin, cysteine-and glycine-rich protein 2, glial fibrillary acidic protein, tissue growth factor b1, matrix metalloproteinases 2 (MMP2) and 13, tissue inhibitor of metalloproteinases 1 and 2 was investigated by real-time PCR. Intracellular signaling pathways of ERK1/2, p38 and, jun-amino-terminal kinase (JNK) were analyzed by western blot analysis. Recombinant HCV core protein induced upregulation of procollagen type I a-1, a-smooth muscle actin, MMP 2 and 13, tissue inhibitor of metalloproteinases 1 and 2, tissue growth factor b1, cysteine-and glycine-rich protein 2, and glial fibrillary acidic protein mRNA expression, whereas HCV envelope 2 protein did not exert any significant effect. Blocking of toll-like receptor 2 (TLR2) with a neutralizing antibody prevented mRNA upregulation by HCV core protein confirming that the TLR2 pathway was involved. Furthermore, western blot analysis revealed HCV-induced phosphorylation of the TLR2-dependent signaling molecules ERK1/2, p38 and JNK mitogen-activated kinases. Our in vitro results demonstrate a direct effect of HCV core protein on activation of HSCs toward a profibrogenic state, which is mediated via the TLR2 pathway. Manipulating the TLR2 pathway may thus provide a new approach for antifibrotic therapies in HCV infection.

show abstract

UV Irradiation Activates JNK and Increases αI(I) Collagen Gene Expression in Rat Hepatic Stellate Cells

Cited by 77 publications

References 33 publications

Cell cycle protein profile of the hepatic stellate cells (HSCs) in dimethylnitrosamine-induced rat hepatic fibrosis

Cell cycle protein profile of the hepatic stellate cells (HSCs) in dimethylnitrosamine-induced rat hepatic fibrosis

Ligands of Peroxisome Proliferator-activated Receptor-γ Block Activation of Pancreatic Stellate Cells

Hepatitis C virus core protein induces fibrogenic actions of hepatic stellate cells via toll-like receptor 2

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