title: Geranylgeranylacetone attenuates hepatic fibrosis by increasing the expression of heat shock protein 70.
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.
authors.affiliation: Department of Gastroenterology, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu 213003, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: He
authors.affiliation: Department of Gastroenterology, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu 213003, P.R. China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhuang
authors.affiliation: Department of Gastroenterology, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu 213003, P.R. China.
authors.forename: Liangzhi
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu 213003, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Qi
authors.affiliation: Department of Gastroenterology, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu 213003, P.R. China.
authors.forename: Binfang
authors.initials: B
authors.lastname: Chen
authors.affiliation: Department of Gastroenterology, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu 213003, P.R. China.
authors.forename: Mei
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu 213003, P.R. China.
authors.forename: Dong
authors.initials: D
authors.lastname: Shao
authors.affiliation: Department of Gastroenterology, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu 213003, P.R. China.
authors.forename: Jianping
authors.initials: J
authors.lastname: Chen
mesh_terms: D000199:Actins / Q000378:metabolism; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001663:Bilirubin / Q000097:blood; D002251:Carbon Tetrachloride; D004195:Disease Models, Animal; D004224:Diterpenes / Q000494:pharmacology*; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006909:Hydroxyproline / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000188:drug therapy*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D000199:Actins; D000410:Alanine Transaminase; D001219:Aspartate Aminotransferases; D001663:Bilirubin; D002251:Carbon Tetrachloride; D004224:Diterpenes; D018840:HSP70 Heat-Shock Proteins; D006909:Hydroxyproline; D053773:Transforming Growth Factor beta1; C508962:Tgfb1 protein, rat; C498862:Acta2 protein, rat; C031049:geranylgeranylacetone