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Geranylgeranylacetone attenuates hepatic fibrosis by increasing the expression of heat shock protein 70.

He W, Zhuang Y, Wang L, Qi L, Chen B, Wang M, Shao D, Chen J - Mol Med Rep (2015)

Bottom Line: The expression levels of α‑smooth muscle actin (α‑SMA) and transforming growth factor‑β1 (TGF‑β1) were determined using immunofluorescence staining and western blotting, and the protein expression levels of HSP70 were determined using western blotting.These changes were attenuated by treatment with GGA.These results demonstrated that GGA exerted beneficial effects in CCl4‑induced liver fibrosis via upregulating the expression of HSP70.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterology, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu 213003, P.R. China.

ABSTRACT
Increasing evidence has demonstrated that the heat shock protein 70 (HSP70) gene may be closely associated with tissue fibrosis; however, the association between HSP70 and liver fibrosis remains to be fully elucidated. The present study hypothesized that geranylgeranylacetone (GGA) exerts beneficial effects on liver fibrosis though upregulation of the expression of HSP70. Liver fibrosis was induced in rats using carbon tetrachloride (CCl4). The rats were subsequently divided into three groups: Control group, CCl4 model group and CCl4 model + GGA group. Liver fibrosis in the rats was evaluated using hematoxylin and eosin staining, Masson's trichrome staining and Sirius red staining. The levels of serum alanine aminotransferase, aspartate aminotransferase and total bilirubin were determined using an automated biochemistry analyzer. The levels of total hepatic hydroxyproline were also determined. The expression levels of α‑smooth muscle actin (α‑SMA) and transforming growth factor‑β1 (TGF‑β1) were determined using immunofluorescence staining and western blotting, and the protein expression levels of HSP70 were determined using western blotting. The CCl4‑induced rats exhibited liver fibrosis, increased hydroxyproline content, impaired liver function, upregulated expression levels of the α‑SMA and TGF‑β1 pro‑fibrogenic proteins, and increased expression of HSP70, compared with the control group. These changes were attenuated by treatment with GGA. These results demonstrated that GGA exerted beneficial effects in CCl4‑induced liver fibrosis via upregulating the expression of HSP70.

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GGA attenuates profibrogenic protein expression in CCl4-induced rats. (A) Immunofluorescence was used to examine the expression levels of TGF-β1 and α-SMA in the liver tissues (magnification, ×200). (B) Protein samples (50 µg) were loaded for western blot analysis of TGF-β1 and α-SMA. Similar results were obtained from three repeated experiments. (C) Quantitative analysis was performed for TGF-β1 and α-SMA using a densitometer. Data are presented as the mean ± standard deviation. #P<0.05, compared with the control group; *P<0.05 compared with the CCl4 group. GGA, geranylgeranylacetone; CCl4, carbon tetrachloride; TGF-β1, transforming growth factor-β1, α-SMA, α-smooth muscle actin.
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f4-mmr-12-04-4895: GGA attenuates profibrogenic protein expression in CCl4-induced rats. (A) Immunofluorescence was used to examine the expression levels of TGF-β1 and α-SMA in the liver tissues (magnification, ×200). (B) Protein samples (50 µg) were loaded for western blot analysis of TGF-β1 and α-SMA. Similar results were obtained from three repeated experiments. (C) Quantitative analysis was performed for TGF-β1 and α-SMA using a densitometer. Data are presented as the mean ± standard deviation. #P<0.05, compared with the control group; *P<0.05 compared with the CCl4 group. GGA, geranylgeranylacetone; CCl4, carbon tetrachloride; TGF-β1, transforming growth factor-β1, α-SMA, α-smooth muscle actin.

Mentions: Immunofluorescence staining and western blotting were used to detect the expression levels of α-SMA and TGF-β1 in the liver tissues of the rats. α-SMA and TGF-β1 have been reported to be involved with the development of hepatic fibrosis (23,24). The expression levels of α-SMA and TGF-β1 were low in the liver tissue of the control rats; however, a significant increase in the expression of α-SMA and TGF-β1 was observed with the development of CCl4-induced hepatic fibrosis. Treatment with GGA was found to markedly reduce the expression levels of hepatic fibrosis-associated proteins (Fig. 4).


Geranylgeranylacetone attenuates hepatic fibrosis by increasing the expression of heat shock protein 70.

He W, Zhuang Y, Wang L, Qi L, Chen B, Wang M, Shao D, Chen J - Mol Med Rep (2015)

GGA attenuates profibrogenic protein expression in CCl4-induced rats. (A) Immunofluorescence was used to examine the expression levels of TGF-β1 and α-SMA in the liver tissues (magnification, ×200). (B) Protein samples (50 µg) were loaded for western blot analysis of TGF-β1 and α-SMA. Similar results were obtained from three repeated experiments. (C) Quantitative analysis was performed for TGF-β1 and α-SMA using a densitometer. Data are presented as the mean ± standard deviation. #P<0.05, compared with the control group; *P<0.05 compared with the CCl4 group. GGA, geranylgeranylacetone; CCl4, carbon tetrachloride; TGF-β1, transforming growth factor-β1, α-SMA, α-smooth muscle actin.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4581808&req=5

f4-mmr-12-04-4895: GGA attenuates profibrogenic protein expression in CCl4-induced rats. (A) Immunofluorescence was used to examine the expression levels of TGF-β1 and α-SMA in the liver tissues (magnification, ×200). (B) Protein samples (50 µg) were loaded for western blot analysis of TGF-β1 and α-SMA. Similar results were obtained from three repeated experiments. (C) Quantitative analysis was performed for TGF-β1 and α-SMA using a densitometer. Data are presented as the mean ± standard deviation. #P<0.05, compared with the control group; *P<0.05 compared with the CCl4 group. GGA, geranylgeranylacetone; CCl4, carbon tetrachloride; TGF-β1, transforming growth factor-β1, α-SMA, α-smooth muscle actin.
Mentions: Immunofluorescence staining and western blotting were used to detect the expression levels of α-SMA and TGF-β1 in the liver tissues of the rats. α-SMA and TGF-β1 have been reported to be involved with the development of hepatic fibrosis (23,24). The expression levels of α-SMA and TGF-β1 were low in the liver tissue of the control rats; however, a significant increase in the expression of α-SMA and TGF-β1 was observed with the development of CCl4-induced hepatic fibrosis. Treatment with GGA was found to markedly reduce the expression levels of hepatic fibrosis-associated proteins (Fig. 4).

Bottom Line: The expression levels of α‑smooth muscle actin (α‑SMA) and transforming growth factor‑β1 (TGF‑β1) were determined using immunofluorescence staining and western blotting, and the protein expression levels of HSP70 were determined using western blotting.These changes were attenuated by treatment with GGA.These results demonstrated that GGA exerted beneficial effects in CCl4‑induced liver fibrosis via upregulating the expression of HSP70.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterology, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu 213003, P.R. China.

ABSTRACT
Increasing evidence has demonstrated that the heat shock protein 70 (HSP70) gene may be closely associated with tissue fibrosis; however, the association between HSP70 and liver fibrosis remains to be fully elucidated. The present study hypothesized that geranylgeranylacetone (GGA) exerts beneficial effects on liver fibrosis though upregulation of the expression of HSP70. Liver fibrosis was induced in rats using carbon tetrachloride (CCl4). The rats were subsequently divided into three groups: Control group, CCl4 model group and CCl4 model + GGA group. Liver fibrosis in the rats was evaluated using hematoxylin and eosin staining, Masson's trichrome staining and Sirius red staining. The levels of serum alanine aminotransferase, aspartate aminotransferase and total bilirubin were determined using an automated biochemistry analyzer. The levels of total hepatic hydroxyproline were also determined. The expression levels of α‑smooth muscle actin (α‑SMA) and transforming growth factor‑β1 (TGF‑β1) were determined using immunofluorescence staining and western blotting, and the protein expression levels of HSP70 were determined using western blotting. The CCl4‑induced rats exhibited liver fibrosis, increased hydroxyproline content, impaired liver function, upregulated expression levels of the α‑SMA and TGF‑β1 pro‑fibrogenic proteins, and increased expression of HSP70, compared with the control group. These changes were attenuated by treatment with GGA. These results demonstrated that GGA exerted beneficial effects in CCl4‑induced liver fibrosis via upregulating the expression of HSP70.

Show MeSH
Related in: MedlinePlus