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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 attenuated CCl4-induced hepatic fibrosis in rats. (A) CCl4 was used to construct a hepatic fibrosis model, to evaluate the therapeutic effect of GGA. Liver sections were stained with HE, Masson's reagent and Sirius Red for histological examination to determine hepatic morphology, structural changes and ECM content in the liver tissue of each group (magnification, ×200). (B and C) Levels of ECM were determined by quantitative estimation of the red-stained areas in the Sirius Red-stained sections, and of hydroxyproline content. #P<0.05, compared with the control group; *P<0.05, compared with the CCl4 group. GGA, geranylgeranylacetone; CCl4, carbon tetrachloride; HE, hematoxylin and eosin; ECM, extracellular matrix.
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f1-mmr-12-04-4895: GGA attenuated CCl4-induced hepatic fibrosis in rats. (A) CCl4 was used to construct a hepatic fibrosis model, to evaluate the therapeutic effect of GGA. Liver sections were stained with HE, Masson's reagent and Sirius Red for histological examination to determine hepatic morphology, structural changes and ECM content in the liver tissue of each group (magnification, ×200). (B and C) Levels of ECM were determined by quantitative estimation of the red-stained areas in the Sirius Red-stained sections, and of hydroxyproline content. #P<0.05, compared with the control group; *P<0.05, compared with the CCl4 group. GGA, geranylgeranylacetone; CCl4, carbon tetrachloride; HE, hematoxylin and eosin; ECM, extracellular matrix.

Mentions: As shown in Fig. 1, the rats in the CCl4-induced group exhibited extensive fibrotic deposition, which was demonstrated by HE, Masson's trichrome and Sirius red staining. In addition, quantitative estimation of hydroxyproline content indicated that the hydroxyproline content was significantly higher in the CCl4-induced group, compared with the control group (P<0.05). However, treatment with GGA resulted in significant decreases in fibrotic deposition and the content of hydroxyproline, compared with the CCl4-induced group (P<0.05).


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 attenuated CCl4-induced hepatic fibrosis in rats. (A) CCl4 was used to construct a hepatic fibrosis model, to evaluate the therapeutic effect of GGA. Liver sections were stained with HE, Masson's reagent and Sirius Red for histological examination to determine hepatic morphology, structural changes and ECM content in the liver tissue of each group (magnification, ×200). (B and C) Levels of ECM were determined by quantitative estimation of the red-stained areas in the Sirius Red-stained sections, and of hydroxyproline content. #P<0.05, compared with the control group; *P<0.05, compared with the CCl4 group. GGA, geranylgeranylacetone; CCl4, carbon tetrachloride; HE, hematoxylin and eosin; ECM, extracellular matrix.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f1-mmr-12-04-4895: GGA attenuated CCl4-induced hepatic fibrosis in rats. (A) CCl4 was used to construct a hepatic fibrosis model, to evaluate the therapeutic effect of GGA. Liver sections were stained with HE, Masson's reagent and Sirius Red for histological examination to determine hepatic morphology, structural changes and ECM content in the liver tissue of each group (magnification, ×200). (B and C) Levels of ECM were determined by quantitative estimation of the red-stained areas in the Sirius Red-stained sections, and of hydroxyproline content. #P<0.05, compared with the control group; *P<0.05, compared with the CCl4 group. GGA, geranylgeranylacetone; CCl4, carbon tetrachloride; HE, hematoxylin and eosin; ECM, extracellular matrix.
Mentions: As shown in Fig. 1, the rats in the CCl4-induced group exhibited extensive fibrotic deposition, which was demonstrated by HE, Masson's trichrome and Sirius red staining. In addition, quantitative estimation of hydroxyproline content indicated that the hydroxyproline content was significantly higher in the CCl4-induced group, compared with the control group (P<0.05). However, treatment with GGA resulted in significant decreases in fibrotic deposition and the content of hydroxyproline, compared with the CCl4-induced group (P<0.05).

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