Acetaldehyde stimulates the activation of latent transforming growth factor-β1 and induces expression of the type II receptor of the cytokine in rat cultured hepatic stellate cells

Chen, Anping

doi:10.1042/bj20020949

Cited by 77 publications

(66 citation statements)

References 47 publications

(99 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Kornek et al have clearly shown, that the addition of alcohol TAA further increases liver injury compared with TAA alone, although features of ALD such as steatosis, Mallory bodies, and "chicken-wire fibrosis" were missing (26). However, rodents are known to be notoriously resistant to fibrosis induction, and most models require addition of a second fibrosis trigger to alcohol administration (26,42); (b) the acetaldehyde concentration of 200 μmol/L causing significant CB1 upregulation in our study is approximately two-fold higher than hepatic concentrations typically encountered in human ALD, but still in the order of what has been described in experimental ALD after dosing rats with different amounts of alcohol (43)(44)(45)(46).…”

Section: Cb1mentioning

confidence: 68%

Cannabinoid Receptor Type I Modulates Alcohol-Induced Liver Fibrosis

Patsenker

Stoll

Millonig

et al. 2011

Mol Med

View full text Add to dashboard Cite

Section: Cb1mentioning

confidence: 68%

Cannabinoid Receptor Type I Modulates Alcohol-Induced Liver Fibrosis

Patsenker

Stoll

Millonig

et al. 2011

Mol Med

View full text Add to dashboard Cite

“…26 Cells were cultured in Dullbecco's modified Eagle's medium (DMEM) with 10% of fetal bovine serum (FBS). Semiconfluent HSC with 4-8 passages were used for experiments.…”

Section: Materials and Methods Materialsmentioning

confidence: 99%

“…26 Proteins were separated by SDS-PAGE with 10% of resolving gel, and transferred to PVDF membrane. Target proteins were respectively detected by primary antibodies against PPARg, phosphorylated types of PDGF-bR, EGFR, ERK1/2, JNK1/2 or AKT, and the corresponding non-phosphorylated types of total proteins; Bcl-2, Bax or cyclin D1, and subsequently by horseradish peroxidase-conjugated secondary antibodies (Santa Cruze Biotechnology, Santa Cruze, CA, USA).…”

Section: Western Blotting Analysesmentioning

confidence: 99%

The interruption of the PDGF and EGF signaling pathways by curcumin stimulates gene expression of PPARγ in rat activated hepatic stellate cell in vitro

Zhou

Zheng

Lin

et al. 2007

Laboratory Investigation

Self Cite

View full text Add to dashboard Cite

Activation of hepatic stellate cells (HSC), the major effector in hepatic fibrogenesis, is coupled with sequential alterations in expression of genes, including the upregulation of platelet-derived growth factor-b receptor (PDGF-bR) and epidermal growth factor receptor (EGFR), as well as the down-regulation of the peroxisome proliferator-activated receptor-g (PPARg). However, the relationship among the alterations in expression of the genes and the activation of their signaling in activated HSC remains obscure. We recently showed that curcumin, the yellow pigment in curry, inhibited cell growth and induced gene expression of endogenous PPARg in activated HSC in vitro. The present study is to elucidate the underlying mechanisms, focusing on the impacts of PDGF and EGF signaling. It is hypothesized that the interruption of the PDGF and EGF signaling pathways by curcumin might stimulate gene expression of PPARg in activated HSC. Our results in this report indicate that the activation of PDGF or EGF signaling by exogenous PDGF or EGF inhibits PPARg gene expression in passaged HSC. Curcumin interrupts PDGF and EGF signaling demonstrated by inhibiting tyrosine phosphorylation of PDGF-bR and EGFR and by reducing the levels of phosphorylated phosphatidylinositol-3 kinase (PI-3K/ AKT), extracellular signal-regulated kinase (ERK) and the Jun N-terminal kinase (JNK). The blockade of PI-3K/AKT, ERK or JNK signaling negatively regulates PPARg gene expression in activated HSC, leading to the reduction in cell growth, including inducing cell arrest and apoptosis. Our results collectively demonstrate that the interruption of the PDGF and EGF signaling pathways by curcumin stimulates gene expression of PPARg in activated HSC. These results provide novel insights into the mechanisms of curcumin in the induction of PPARg gene expression in activated HSC.

show abstract

“…Acetaldehyde was shown increase secretion of TGF-␤ by stellate cells and to increase expression of the type II TGF-␤ receptor (33). Neutralizing antibody to TGF-␤ decreased acetaldehyde-induced augmentation of the mouse ␣ 2 (I) collagen mRNA in stellate cells (13).…”

Section: The Activating Effect Of Acetaldehyde On Enhancing the Activmentioning

confidence: 99%

Identification of a Novel NF-κB-binding Site with Regulation of the Murine α2(I) Collagen Promoter

Novitskiy

Potter

Rennie-Tankersley

et al. 2004

Journal of Biological Chemistry

View full text Add to dashboard Cite

Hepatic fibrosis is due to the increased synthesis and deposition of type I collagen. Acetaldehyde activates type I collagen promoters. Nuclear factor B (NF-B) was previously shown to inhibit expression of murine ␣ 1 (I) and human ␣ 2 (I) collagen promoters. The present study identifies binding of NF-B, present in nuclear extracts of stellate cells, to a region between ؊553 and ؊537 of the murine ␣ 2 (I) collagen promoter. The NF-B (p65) expression vector inhibited promoter activity. Mutation of the promoter at the NF-B-binding site increased basal promoter activity and abrogated the activating and inhibitory effects of transforming growth factor ␤ and tumor necrosis factor ␣, respectively, on promoter activity. Acetaldehyde increased I B-␣ kinase activity and phosphorylated I B-␣, NF-B nuclear protein, and its binding to the promoter. However, the activating effect of acetaldehyde was not affected by the mutation of the promoter. In conclusion, although acetaldehyde increases the binding of NF-B to the murine ␣ 2 (I) collagen promoter, this binding does not mediate the activating effect of acetaldehyde on promoter activity. The effects of acetaldehyde in increasing the translocation of NF-B to the nucleus with increased DNA binding activity may be important in mediating the effects of acetaldehyde on other genes.

show abstract

Acetaldehyde stimulates the activation of latent transforming growth factor-β1 and induces expression of the type II receptor of the cytokine in rat cultured hepatic stellate cells

Cited by 77 publications

References 47 publications

Cannabinoid Receptor Type I Modulates Alcohol-Induced Liver Fibrosis

Cannabinoid Receptor Type I Modulates Alcohol-Induced Liver Fibrosis

The interruption of the PDGF and EGF signaling pathways by curcumin stimulates gene expression of PPARγ in rat activated hepatic stellate cell in vitro

Identification of a Novel NF-κB-binding Site with Regulation of the Murine α2(I) Collagen Promoter

Contact Info

Product

Resources

About