Limits...
NF-κB inhibition alleviates carbon tetrachloride-induced liver fibrosis via suppression of activated hepatic stellate cells.

Wang F, Liu S, DU T, Chen H, Li Z, Yan J - Exp Ther Med (2014)

Bottom Line: BAY effectively decreased the cell viability of activated HSC-T6 cells and suppressed HSC-T6 activation by downregulating the expression of collagen I and α-smooth muscle actin.BAY significantly inhibited the phosphorylation of phosphatidylinositol 3-kinase (PI3K) and serine/threonine kinase-protein kinase B (Akt) in activated HSC-T6 cells.Therefore, the results of the present study demonstrate that BAY attenuates liver fibrosis by blocking PI3K and Akt phosphorylation in activated HSCs.

View Article: PubMed Central - PubMed

Affiliation: Department of General Surgery Ward 1, Xinxiang Central Hospital, Xinxiang, Henan 453000, P.R. China.

ABSTRACT
An effective treatment for hepatic fibrosis is not available clinically. Nuclear factor (NF)-κB plays a central role in inflammation and fibrosis. The aim of the present study was to investigate the effect of an NF-κB inhibitor, BAY-11-7082 (BAY), on mouse liver fibrosis. The effects of BAY on hepatic stellate cell (HSC) activation were measured in the lipopolysaccharide-activated rat HSC-T6 cell line. In addition, the therapeutic effect of BAY was studied in vivo using a model of hepatic fibrosis induced by carbon tetrachloride (CCl4) in mice. BAY effectively decreased the cell viability of activated HSC-T6 cells and suppressed HSC-T6 activation by downregulating the expression of collagen I and α-smooth muscle actin. BAY significantly inhibited the phosphorylation of phosphatidylinositol 3-kinase (PI3K) and serine/threonine kinase-protein kinase B (Akt) in activated HSC-T6 cells. In addition, administration of BAY attenuated mouse liver fibrosis induced by CCl4, as shown by histology and the expression of profibrogenic markers. BAY also significantly decreased the levels of serum alanine aminotransferase in this model of hepatic fibrosis. Therefore, the results of the present study demonstrate that BAY attenuates liver fibrosis by blocking PI3K and Akt phosphorylation in activated HSCs. Thus, BAY demonstrates therapeutic potential as a treatment for hepatic fibrosis.

No MeSH data available.


Related in: MedlinePlus

Effect of BAY on the protein expression levels of collagen I and α-SMA in CCl4-induced mouse liver injury. CCl4-induced liver injury revealed high expression levels of collagen I and α-SMA by western blotting. BAY decreased the protein expression levels of collagen I and α-SMA in the liver injury model. The in vivo data were consistent with the in vitro results. #P<0.01, vs. control; *P<0.01, vs. CCl4. BAY, BAY-11–7082; SMA, smooth muscle actin; CCl4, carbon tetrachloride.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4061207&req=5

f5-etm-08-01-0095: Effect of BAY on the protein expression levels of collagen I and α-SMA in CCl4-induced mouse liver injury. CCl4-induced liver injury revealed high expression levels of collagen I and α-SMA by western blotting. BAY decreased the protein expression levels of collagen I and α-SMA in the liver injury model. The in vivo data were consistent with the in vitro results. #P<0.01, vs. control; *P<0.01, vs. CCl4. BAY, BAY-11–7082; SMA, smooth muscle actin; CCl4, carbon tetrachloride.

Mentions: Serum ALT levels were determined as an indicator of liver function and the ability of BAY to reduce serum ALT levels in CCl4-induced liver injury was investigated. ALT levels were significantly elevated in the CCl4 group (Group 1 vs. Group 2, 38.96±5.88 vs. 448.45±78.40 U/l; P<0.001). However, BAY treatment significantly attenuated the CCl4-induced increase in ALT levels (Group 2 vs. Group 3, 448.45±78.40 vs. 361.37±82.51 U/l; P<0.001). In addition, CCl4-induced liver injury revealed high expression levels of collagen I and α-SMA by western blotting (Fig. 5) and BAY was shown to decrease the protein expression levels of collagen I and α-SMA in the liver injury model. These in vivo results were consistent with the in vitro results.


NF-κB inhibition alleviates carbon tetrachloride-induced liver fibrosis via suppression of activated hepatic stellate cells.

Wang F, Liu S, DU T, Chen H, Li Z, Yan J - Exp Ther Med (2014)

Effect of BAY on the protein expression levels of collagen I and α-SMA in CCl4-induced mouse liver injury. CCl4-induced liver injury revealed high expression levels of collagen I and α-SMA by western blotting. BAY decreased the protein expression levels of collagen I and α-SMA in the liver injury model. The in vivo data were consistent with the in vitro results. #P<0.01, vs. control; *P<0.01, vs. CCl4. BAY, BAY-11–7082; SMA, smooth muscle actin; CCl4, carbon tetrachloride.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4061207&req=5

f5-etm-08-01-0095: Effect of BAY on the protein expression levels of collagen I and α-SMA in CCl4-induced mouse liver injury. CCl4-induced liver injury revealed high expression levels of collagen I and α-SMA by western blotting. BAY decreased the protein expression levels of collagen I and α-SMA in the liver injury model. The in vivo data were consistent with the in vitro results. #P<0.01, vs. control; *P<0.01, vs. CCl4. BAY, BAY-11–7082; SMA, smooth muscle actin; CCl4, carbon tetrachloride.
Mentions: Serum ALT levels were determined as an indicator of liver function and the ability of BAY to reduce serum ALT levels in CCl4-induced liver injury was investigated. ALT levels were significantly elevated in the CCl4 group (Group 1 vs. Group 2, 38.96±5.88 vs. 448.45±78.40 U/l; P<0.001). However, BAY treatment significantly attenuated the CCl4-induced increase in ALT levels (Group 2 vs. Group 3, 448.45±78.40 vs. 361.37±82.51 U/l; P<0.001). In addition, CCl4-induced liver injury revealed high expression levels of collagen I and α-SMA by western blotting (Fig. 5) and BAY was shown to decrease the protein expression levels of collagen I and α-SMA in the liver injury model. These in vivo results were consistent with the in vitro results.

Bottom Line: BAY effectively decreased the cell viability of activated HSC-T6 cells and suppressed HSC-T6 activation by downregulating the expression of collagen I and α-smooth muscle actin.BAY significantly inhibited the phosphorylation of phosphatidylinositol 3-kinase (PI3K) and serine/threonine kinase-protein kinase B (Akt) in activated HSC-T6 cells.Therefore, the results of the present study demonstrate that BAY attenuates liver fibrosis by blocking PI3K and Akt phosphorylation in activated HSCs.

View Article: PubMed Central - PubMed

Affiliation: Department of General Surgery Ward 1, Xinxiang Central Hospital, Xinxiang, Henan 453000, P.R. China.

ABSTRACT
An effective treatment for hepatic fibrosis is not available clinically. Nuclear factor (NF)-κB plays a central role in inflammation and fibrosis. The aim of the present study was to investigate the effect of an NF-κB inhibitor, BAY-11-7082 (BAY), on mouse liver fibrosis. The effects of BAY on hepatic stellate cell (HSC) activation were measured in the lipopolysaccharide-activated rat HSC-T6 cell line. In addition, the therapeutic effect of BAY was studied in vivo using a model of hepatic fibrosis induced by carbon tetrachloride (CCl4) in mice. BAY effectively decreased the cell viability of activated HSC-T6 cells and suppressed HSC-T6 activation by downregulating the expression of collagen I and α-smooth muscle actin. BAY significantly inhibited the phosphorylation of phosphatidylinositol 3-kinase (PI3K) and serine/threonine kinase-protein kinase B (Akt) in activated HSC-T6 cells. In addition, administration of BAY attenuated mouse liver fibrosis induced by CCl4, as shown by histology and the expression of profibrogenic markers. BAY also significantly decreased the levels of serum alanine aminotransferase in this model of hepatic fibrosis. Therefore, the results of the present study demonstrate that BAY attenuates liver fibrosis by blocking PI3K and Akt phosphorylation in activated HSCs. Thus, BAY demonstrates therapeutic potential as a treatment for hepatic fibrosis.

No MeSH data available.


Related in: MedlinePlus