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

  • Authors:
    • Wei He
    • Yun Zhuang
    • Liangzhi Wang
    • Lei Qi
    • Binfang Chen
    • Mei Wang
    • Dong Shao
    • Jianping Chen
  • View Affiliations / Copyright

    Affiliations: Department of Gastroenterology, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu 213003, P.R. China
    Copyright: © He et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 4895-4900
    |
    Published online on: July 9, 2015
       https://doi.org/10.3892/mmr.2015.4069
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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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1 

Bellaye PS, Burgy O, Causse S, Garrido C and Bonniaud P: Heat shock proteins in fibrosis and wound healing: Good or evil? Pharmacol Ther. 143:119–132. 2014. View Article : Google Scholar : PubMed/NCBI

2 

Booz GW, Carl LL and Baker KM: Amplification of angiotensin II signaling in cardiac myocytes by adenovirus-mediated overex-pression of the AT1 receptor: Ann NY. Acad Sci. 874:20–26. 1999. View Article : Google Scholar

3 

Bukau B and Horwich AL: The Hsp70 and Hsp60 chaperone machines. Cell. 92:351–366. 1998. View Article : Google Scholar : PubMed/NCBI

4 

Friedman SL: Molecular regulation of hepatic fibrosis, an integrated cellular response to tissue injury. J Biol Chem. 275:2247–2250. 2000. View Article : Google Scholar : PubMed/NCBI

5 

Friedman SL: Hepatic stellate cells: Protean, multifunctional, and enigmatic cells of the liver. Physiol Rev. 88:125–172. 2008. View Article : Google Scholar : PubMed/NCBI

6 

Shiber A and Ravid T: Chaperoning proteins for destruction: Diverse roles of Hsp70 chaperones and their co-chaperones in targeting misfolded proteins to the proteasome. Biomolecules. 4:704–724. 2014. View Article : Google Scholar : PubMed/NCBI

7 

Fudaba Y, Ohdan H, Tashiro H, Mizunuma K, Ito H, Fukuda Y, Dohi K and Asahara T: High dose of geranylgeranylacetone accumulate HSP72 mRNA in rat liver. Transplant Proc. 33:9782001. View Article : Google Scholar : PubMed/NCBI

8 

Reus IS, Bando I, Andres D and Cascales M: Relationship between expression of HSP70 and metallothionein and oxidative stress during mercury chloride induced acute liver injury in rats. J Biochem Mol Toxicol. 17:161–168. 2003. View Article : Google Scholar : PubMed/NCBI

9 

Fudaba Y, Tashiro H, Ohdan H, Miyata Y, Shibata S, Shintaku S, Nishihara M, Asahara T, Ito H, Fukuda Y and Dohi K: Efficacy of HSP72 induction in rat liver by orally administered geranylgeranylacetone. Transpl Int. 13(Suppl 1): S278–S281. 2000. View Article : Google Scholar : PubMed/NCBI

10 

Fujibayashi T, Hashimoto N, Jijiwa M, Hasegawa Y, Kojima T and Ishiguro N: Protective effect of geranylgeranylacetone, an inducer of heat shock protein 70, against drug-induced lung injury/fibrosis in an animal model. BMC Pulm Med. 9:452009. View Article : Google Scholar : PubMed/NCBI

11 

Goette A, Staack T, Röcken C, Arndt M, Geller JC, Huth C, Ansorge S, Klein HU and Lendeckel U: Increased expression of extracellular signal-regulated kinase and angiotensin-converting enzyme in human atria during atrial fibrillation. J Am Coll Cardiol. 35:1669–1677. 2000. View Article : Google Scholar : PubMed/NCBI

12 

González-Ramos M, Calleros L, López-Ongil S, Raoch V, Griera M, Rodríguez-Puyol M, de Frutos S and Rodríguez-Puyol D: HSP70 increases extracellular matrix production by human vascular smooth muscle through TGF-β1 up-regulation. Int J Biochem Cell Biol. 45:232–242. 2013. View Article : Google Scholar

13 

Kahloon RA, Xue J, Bhargava A, Csizmadia E, Otterbein L, Kass DJ, Bon J, Soejima M, Levesque MC, Lindell KO, et al: Patients with idiopathic pulmonary fibrosis with antibodies to heat shock protein 70 have poor prognoses. Am J Respir Crit Care Med. 187:768–775. 2013. View Article : Google Scholar :

14 

Kanemura H, Kusumoto K, Miyake H, Tashiro S, Rokutan K and Shimada M: Geranylgeranylacetone prevents acute liver damage after massive hepatectomy in rats through suppression of a CXC chemokine GRO1 and induction of heat shock proteins. J Gastrointest Surg. 13:66–73. 2009. View Article : Google Scholar

15 

Lee UE and Friedman SL: Mechanisms of hepatic fibrogenesis. Best Pract Res Clin Gastroenterol. 25:195–206. 2011. View Article : Google Scholar : PubMed/NCBI

16 

Luo FC, Zhao L, Deng J, Liang M, Zeng XS, Liu H and Bai J: Geranylgeranylacetone protects against morphine-induced hepatic and renal damage in mice. Mol Med Rep. 7:694–700. 2013.

17 

Mao H, Li Z, Zhou Y, Li Z, Zhuang S, An X, Zhang B, Chen W, Nie J, Wang Z, et al: HSP72 attenuates renal tubular cell apoptosis and interstitial fibrosis in obstructive nephropathy. Am J Physiol Renal Physiol. 295:F202–F214. 2008. View Article : Google Scholar : PubMed/NCBI

18 

Myung SJ, Yoon JH, Kim BH, Lee JH, Jung EU and Lee HS: Heat shock protein 90 inhibitor induces apoptosis and attenuates activation of hepatic stellate cells. J Pharmacol Exp Ther. 330:276–282. 2009. View Article : Google Scholar : PubMed/NCBI

19 

Ooie T, Takahashi N, Saikawa T, Nawata T, Arikawa M, Yamanaka K, Hara M, Shimada T and Sakata T: Single oral dose of geranylgeranylacetone induces heat-shock protein 72 and renders protection against ischemia/reperfusion injury in rat heart. Circulation. 104:1837–1843. 2001. View Article : Google Scholar : PubMed/NCBI

20 

Routsias JG and Tzioufas AG: The role of chaperone proteins in autoimmunity. Ann NY Acad Sci. 1088:52–64. 2006. View Article : Google Scholar : PubMed/NCBI

21 

Takahashi N, Kume O, Wakisaka O, Fukunaga N, Teshima Y, Hara M and Saikawa T: Novel strategy to prevent atrial fibrosis and fibrillation. Circ J. 76:2318–2326. 2012. View Article : Google Scholar : PubMed/NCBI

22 

Chen J: Chloroquine improved carbon tetrachloride-induced liver fibrosis through its inhibition of the activation of hepatic stellate cells: Role of autophagy. Biol Pharm Bull. 37:1505–1509. 2014. View Article : Google Scholar : PubMed/NCBI

23 

Nouchi T, Tanaka Y, Tsukada T, Sato C and Marumo F: Appearance of alpha-smooth-muscle-actin-positive cells in hepatic fibrosis. Liver. 11:100–105. 1991. View Article : Google Scholar : PubMed/NCBI

24 

Hellerbrand C, Stefanovic B, Giordano F, Burchardt ER and Brenner DA: The role of TGFbeta1 in initiating hepatic stellate cell activation in vivo. J Hepatol. 30:77–87. 1999. View Article : Google Scholar : PubMed/NCBI

25 

Tanaka K, Tanaka Y, Namba T, Azuma A and Mizushima T: Heat shock protein 70 protects against bleomycin-induced pulmonary fibrosis in mice. Biochem Pharmacol. 80:920–931. 2010. View Article : Google Scholar : PubMed/NCBI

26 

Shin Y, Klucken J, Patterson C, Hyman BT and McLean PJ: The co-chaperone carboxyl terminus of Hsp70-interacting protein (CHIP) mediates alpha-synuclein degradation decisions between proteasomal and lysosomal pathways. J Biol Chem. 280:23727–23734. 2005. View Article : Google Scholar : PubMed/NCBI

27 

Tsuruma T, Yagihashi A, Koide S, Araya J, Tarumi K, Watanabe N and Hirata K: Geranylgeranylacetone induces heat shock protein-73 in rat small intestine. Transplant Proc. 31:572–573. 1999. View Article : Google Scholar : PubMed/NCBI

28 

Wakisaka O, Takahashi N, Shinohara T, Ooie T, Nakagawa M, Yonemochi H, Hara M, Shimada T, Saikawa T and Yoshimatsu H: Hyperthermia treatment prevents angiotensin II-mediated atrial fibrosis and fibrillation via induction of heat-shock protein 72. J Mol Cell Cardiol. 43:616–626. 2007. View Article : Google Scholar : PubMed/NCBI

29 

Wu C: Heat shock transcription factors: Structure and regulation. Annu Rev Cell Dev Biol. 11:441–469. 1995. View Article : Google Scholar : PubMed/NCBI

30 

Wynn TA: Common and unique mechanisms regulate fibrosis in various fibroproliferative diseases. J Clin Invest. 117:524–529. 2007. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
He W, Zhuang Y, Wang L, Qi L, Chen B, Wang M, Shao D and Chen J: Geranylgeranylacetone attenuates hepatic fibrosis by increasing the expression of heat shock protein 70. Mol Med Rep 12: 4895-4900, 2015.
APA
He, W., Zhuang, Y., Wang, L., Qi, L., Chen, B., Wang, M. ... Chen, J. (2015). Geranylgeranylacetone attenuates hepatic fibrosis by increasing the expression of heat shock protein 70. Molecular Medicine Reports, 12, 4895-4900. https://doi.org/10.3892/mmr.2015.4069
MLA
He, W., Zhuang, Y., Wang, L., Qi, L., Chen, B., Wang, M., Shao, D., Chen, J."Geranylgeranylacetone attenuates hepatic fibrosis by increasing the expression of heat shock protein 70". Molecular Medicine Reports 12.4 (2015): 4895-4900.
Chicago
He, W., Zhuang, Y., Wang, L., Qi, L., Chen, B., Wang, M., Shao, D., Chen, J."Geranylgeranylacetone attenuates hepatic fibrosis by increasing the expression of heat shock protein 70". Molecular Medicine Reports 12, no. 4 (2015): 4895-4900. https://doi.org/10.3892/mmr.2015.4069
Copy and paste a formatted citation
x
Spandidos Publications style
He W, Zhuang Y, Wang L, Qi L, Chen B, Wang M, Shao D and Chen J: Geranylgeranylacetone attenuates hepatic fibrosis by increasing the expression of heat shock protein 70. Mol Med Rep 12: 4895-4900, 2015.
APA
He, W., Zhuang, Y., Wang, L., Qi, L., Chen, B., Wang, M. ... Chen, J. (2015). Geranylgeranylacetone attenuates hepatic fibrosis by increasing the expression of heat shock protein 70. Molecular Medicine Reports, 12, 4895-4900. https://doi.org/10.3892/mmr.2015.4069
MLA
He, W., Zhuang, Y., Wang, L., Qi, L., Chen, B., Wang, M., Shao, D., Chen, J."Geranylgeranylacetone attenuates hepatic fibrosis by increasing the expression of heat shock protein 70". Molecular Medicine Reports 12.4 (2015): 4895-4900.
Chicago
He, W., Zhuang, Y., Wang, L., Qi, L., Chen, B., Wang, M., Shao, D., Chen, J."Geranylgeranylacetone attenuates hepatic fibrosis by increasing the expression of heat shock protein 70". Molecular Medicine Reports 12, no. 4 (2015): 4895-4900. https://doi.org/10.3892/mmr.2015.4069
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