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Transforming growth factor‑β1 reduces apoptosis via autophagy activation in hepatic stellate cells

  • Authors:
    • Mei‑Ya Fu
    • Ya‑Jun He
    • Xia Lv
    • Zhi‑He Liu
    • Yan Shen
    • Guo‑Rong  Ye
    • Yan‑Mei Deng
    • Jian‑Chang Shu
  • View Affiliations / Copyright

    Affiliations: Department of Gastroenterology, The Fourth Affiliated Hospital of the Medical College of Jinan University, Guangzhou Red Cross Hospital, Guangzhou, Guangdong 510220, P.R. China
    Copyright: © Fu et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].
  • Pages: 1282-1288
    |
    Published online on: July 15, 2014
       https://doi.org/10.3892/mmr.2014.2383
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Abstract

Autophagy is a metabolic process that is important in fibrogenesis, in which cellular components are degraded by lysosomal machinery. Transforming growth factor β1 (TGF‑β1) is a potent fibrogenic cytokine involved in liver fibrosis; however, it remains elusive whether autophagy is regulated by TGF‑β1 in this process. In the present study, the function of TGF‑β1‑mediated autophagy in the proliferation and apoptosis of hepatic stellate cells (HSCs) was investigated. A rat HSC cell line (HSC‑T6) was incubated with or without TGF‑β1 followed by bafilomycin A1, and microtubule-associated proteins 1A/1B light chain 3 (LC3) small interfering (si)RNA was used to inhibit autophagy in order to assess the association between TGF‑β1 and autophagy. HSC‑T6 cell transient transfection was accomplished with a pLVX‑AcGFP‑N1‑rLC3B‑encoding plasmid. An MTS assay and flow cytometry were utilized to detect proliferation and apoptosis of HSC‑T6 cells. Quantitative polymerase chain reaction, immunofluorescence and western blot analysis were used to detect the presence of activation markers. Proliferation was increased and apoptosis was reduced in HSC‑T6 cells treated with TGF‑β1 compared with cells subjected to serum deprivation. However, when HSC‑T6 cells were treated with bafilomycin A1 and LC3 siRNA, increased apoptosis and reduced proliferation were observed. In addition, protein and mRNA expression levels of the autophagy marker LC3 were significantly increased. GFP‑LC3 punctate markings were more prolific following TGF‑β1 treatment of HSC‑T6 cells, indicating that TGF‑β1 may rescue HSC‑T6 cells from serum deprivation and reduce apoptosis via autophagy induction. The present study elucidated the possible functions of TGF‑β1‑mediated autophagy in the pathological process of liver fibrosis.
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1 

Ni HM, Williams JA, Yang H, Shi YH, Fan J and Ding WX: Targeting autophagy for the treatment of liver diseases. Pharmacol Res. 66:463–474. 2012. View Article : Google Scholar : PubMed/NCBI

2 

Klionsky DJ: The autophagy connection. Dev Cell. 19:11–12. 2010. View Article : Google Scholar

3 

González-Polo RA, Boya P, Pauleau AL, et al: The apoptosis/autophagy paradox: autophagic vacuolization before apoptotic death. J Cell Sci. 118:3091–3102. 2005.PubMed/NCBI

4 

Komatsu M: Liver autophagy: physiology and pathology. J Bio Chem. 152:5–15. 2012.PubMed/NCBI

5 

Sasaki M, Miyakoshi M, Sato Y and Nakanuma Y: Autophagy may precede cellular senescence of bile ductular cells in ductular reaction in primary biliary cirrhosis. Dig Dis Sci. 57:660–666. 2012. View Article : Google Scholar

6 

Bhogal RH and Afford SC: Autophagy and the Liver. Autophagy - A Double-Edged Sword - Cell Survival or Death? Bailly Yannick: InTech; Rijeka, Croatia: pp. 165–185. 2013

7 

Rautou PE, Mansouri A, Lebrec D, Durand F, Valla D and Moreau R: Autophagy in liver diseases. J Hepatol. 53:1123–1134. 2010. View Article : Google Scholar

8 

Hilscher M, Hernandez-Gea V and Friedman SL: Autophagy and mesenchymal cell fibrogenesis. Biochim Biophys Acta. 1831.972–978. 2012.PubMed/NCBI

9 

Hidvegi T, Ewing M, Hale P, et al: An autophagy-enhancing drug promotes degradation of mutant alpha1-antitrypsin Z and reduces hepatic fibrosis. Science. 329:229–232. 2010. View Article : Google Scholar : PubMed/NCBI

10 

Kim SI, Na HJ, Ding Y, Wang Z, Lee SJ and Choi ME: Autophagy promotes intracellular degradation of type I collagen induced by transforming growth factor (TGF)-β1. J Biol Chem. 287:11677–11688. 2012.PubMed/NCBI

11 

Hernández-Gea V, Ghiassi-Nejad Z, Rozenfeld R, et al: Autophagy releases lipid that promotes fibrogenesis by activated hepatic stellate cells in mice and in human tissues. Gastroenterology. 142:938–946. 2012.PubMed/NCBI

12 

Thoen LF, Guimarães EL, Dollé L, et al: A role for autophagy during hepatic stellate cell activation. J Hepatol. 55:1353–1360. 2011. View Article : Google Scholar : PubMed/NCBI

13 

Yin XM, Ding WX and Gao W: Autophagy in the liver. Hepatology. 47:1773–1785. 2008. View Article : Google Scholar : PubMed/NCBI

14 

Rubinsztein DC, Gestwicki JE, Murphy LO and Klionsky DJ: Potential therapeutic applications of autophagy. Nat Rev Drug Discov. 6:304–312. 2007. View Article : Google Scholar : PubMed/NCBI

15 

Deretic V and Levine B: Autophagy, immunity and microbial adaptations. Cell Host Microbe. 5:527–549. 2009. View Article : Google Scholar : PubMed/NCBI

16 

Friedman SL: Hepatic fibrosis - overview. Toxicology. 254:120–129. 2008. View Article : Google Scholar

17 

Brenner DA: Molecular pathogenesis of liver fibrosis. Trans Am Clin Climatol Assoc. 120:361–368. 2009.PubMed/NCBI

18 

Iimuro Y and Brenner DA: Matrix metalloproteinase gene delivery for liver fibrosis. Pharm Res. 25:249–258. 2008. View Article : Google Scholar : PubMed/NCBI

19 

Gajewska M, Gajkowska B and Motyl T: Apoptosis and autophagy induced by TGF-β1 in bovine mammary epithelial BME-UV1 cells. J Physiol Pharmacol. 56(Suppl 3): 143–157. 2005.

20 

Ding Y, Kim JK, Kim SI, Na HJ, Jun SY, Lee SJ and Choi ME: TGF-{beta}1 protects against mesangial cell apoptosis via induction of autophagy. J Biol Chem. 285:37909–37919. 2010. View Article : Google Scholar : PubMed/NCBI

21 

Klionsky DJ, Abdalla FC, Abeliovich H, et al: Guidelines for the use and interpretation of assays for monitoring autophagy. Autophagy. 8:445–544. 2012. View Article : Google Scholar

22 

Leask A and Abraham DJ: TGF beta signaling and the fibrotic response. FASEB J. 18:816–827. 2004. View Article : Google Scholar : PubMed/NCBI

23 

Nakerakanti S and Trojanowska M: The role of TGF-β receptors in fibrosis. Open Rheumatol J. 6:156–162. 2012.

24 

Roberts AB: Molecular and cell biology of TGF-beta. Miner Electrolyte Metab. 24:111–119. 1998. View Article : Google Scholar

25 

Roberts AB and Sporn MB: Physiological actions and clinical applications of transforming growth factor-beta (TGF-beta). Growth Factors. 8:1–9. 1993. View Article : Google Scholar : PubMed/NCBI

26 

Brown TL, Patil S, Cianci CD, Morrow JS and Howe PH: Transforming growth factor-beta induces caspase 3-independent cleavage of alphaII-spectrin (alpha-fodrin) coincident with apoptosis. J Biol Chem. 274:23256–23262. 1999. View Article : Google Scholar : PubMed/NCBI

27 

Dai C, Yang J and Liu Y: Transforming growth factor-beta1 potentiates renal tubular epithelial cell death by a mechanism independent of Smad signaling. J Biol Chem. 278:12537–12545. 2003. View Article : Google Scholar : PubMed/NCBI

28 

Chin BY, Petrache I, Choi AM and Choi ME: Transforming growth factor beta1 rescues serum deprivation-induced apoptosis via the mitogen-activated protein kinase (MAPK) pathway in macrophages. J Biol Chem. 274:11362–11368. 1999. View Article : Google Scholar : PubMed/NCBI

29 

Hara T, Kamura T and Nakayama K, Oshikawa K, Hatakeyama S and Nakayama K: Degradation of p27(Kip1) at the G(0)–G(1) transition mediated by a Skp2-independent ubiquitination pathway. J Biol Chem. 276:48937–48943. 2001.PubMed/NCBI

30 

Chen HH, Zhao S and Song JG: TGF-beta1 suppresses apoptosis via differential regulation of MAP kinases and ceramide production. Cell Death Differ. 10:516–527. 2003. View Article : Google Scholar : PubMed/NCBI

31 

Maiuri MC, Zalckvar E, Kimchi A and Kroemer G: Self-eating and self-killing: crosstalk between autophagy and apoptosis. Nat Rev Mol Cell Biol. 8:741–752. 2007. View Article : Google Scholar : PubMed/NCBI

32 

Wang RC and Levine B: Autophagy in cellular growth control. FEBS Lett. 584:1417–1426. 2010. View Article : Google Scholar : PubMed/NCBI

33 

Suzuki HI, Kiyono K and Miyazono K: Regulation of autophagy by transforming growth factor-β (TGF-β) signaling. Autophagy. 6:645–647. 2010.

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Copy and paste a formatted citation
Spandidos Publications style
Fu MY, He YJ, Lv X, Liu ZH, Shen Y, Ye GR, Deng YM and Shu JC: Transforming growth factor‑β1 reduces apoptosis via autophagy activation in hepatic stellate cells. Mol Med Rep 10: 1282-1288, 2014.
APA
Fu, M., He, Y., Lv, X., Liu, Z., Shen, Y., Ye, G. ... Shu, J. (2014). Transforming growth factor‑β1 reduces apoptosis via autophagy activation in hepatic stellate cells. Molecular Medicine Reports, 10, 1282-1288. https://doi.org/10.3892/mmr.2014.2383
MLA
Fu, M., He, Y., Lv, X., Liu, Z., Shen, Y., Ye, G., Deng, Y., Shu, J."Transforming growth factor‑β1 reduces apoptosis via autophagy activation in hepatic stellate cells". Molecular Medicine Reports 10.3 (2014): 1282-1288.
Chicago
Fu, M., He, Y., Lv, X., Liu, Z., Shen, Y., Ye, G., Deng, Y., Shu, J."Transforming growth factor‑β1 reduces apoptosis via autophagy activation in hepatic stellate cells". Molecular Medicine Reports 10, no. 3 (2014): 1282-1288. https://doi.org/10.3892/mmr.2014.2383
Copy and paste a formatted citation
x
Spandidos Publications style
Fu MY, He YJ, Lv X, Liu ZH, Shen Y, Ye GR, Deng YM and Shu JC: Transforming growth factor‑β1 reduces apoptosis via autophagy activation in hepatic stellate cells. Mol Med Rep 10: 1282-1288, 2014.
APA
Fu, M., He, Y., Lv, X., Liu, Z., Shen, Y., Ye, G. ... Shu, J. (2014). Transforming growth factor‑β1 reduces apoptosis via autophagy activation in hepatic stellate cells. Molecular Medicine Reports, 10, 1282-1288. https://doi.org/10.3892/mmr.2014.2383
MLA
Fu, M., He, Y., Lv, X., Liu, Z., Shen, Y., Ye, G., Deng, Y., Shu, J."Transforming growth factor‑β1 reduces apoptosis via autophagy activation in hepatic stellate cells". Molecular Medicine Reports 10.3 (2014): 1282-1288.
Chicago
Fu, M., He, Y., Lv, X., Liu, Z., Shen, Y., Ye, G., Deng, Y., Shu, J."Transforming growth factor‑β1 reduces apoptosis via autophagy activation in hepatic stellate cells". Molecular Medicine Reports 10, no. 3 (2014): 1282-1288. https://doi.org/10.3892/mmr.2014.2383
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