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Bcl-2 overexpression in hepatic stellate cell line CFSC-2G, induces a pro-fibrotic state.
J Gastroenterol Hepatol. 2010 Jul; 25(7):1306-14.JG

Abstract

BACKGROUND AND AIM

Development of hepatic fibrosis is a complex process that involves oxidative stress (OS) and an altered balance between pro- and anti-apoptotic molecules. Since Bcl-2 overexpression preserves viability against OS, our objective was to address the effect of Bcl-2 overexpression in the hepatic stellate cells (HSC) cell-line CFSC-2G under acetaldehyde and H(2)O(2) challenge, and explore if it protects these cells against OS, induces replicative senescence and/or modify extracellular matrix (ECM) remodeling potential.

METHODS

To induce Bcl-2 overexpression, HSC cell line CFSC-2G was transfected by lipofection technique. Green fluorescent protein-only CFSC-2G cells were used as a control. Cell survival after H(2)O(2) treatment and total protein oxidation were assessed. To determine cell cycle arrest, proliferation-rate, DNA synthesis and senescence were assessed. Matrix metalloproteinases (MMP), tissue-inhibitor of MMP (TIMP), transglutaminases (TG) and smooth muscle a-actin (alpha-SMA) were evaluated by western blot in response to acetaldehyde treatment as markers of ECM remodeling capacity in addition to transforming growth factor-beta (TGF-beta) mRNA.

RESULTS

Cells overexpressing Bcl-2 survived approximately 20% more than control cells when exposed to H(2)O(2) and approximately 35% proteins were protected from oxidation, but Bcl-2 did not slow proliferation or induced senescence. Bcl-2 overexpression did not change alpha-SMA levels, but it increased TIMP-1 (55%), tissue transglutaminases (tTG) (25%) and TGF-beta mRNA (49%), when exposed to acetaldehyde, while MMP-13 content decreased (47%).

CONCLUSIONS

Bcl-2 overexpression protected HSC against oxidative stress but it did not induce replicative senescence. It increased TIMP-1, tTG and TGF-beta mRNA levels and decreased MMP-13 content, suggesting that Bcl-2 overexpression may play a key role in the progression of fibrosis in chronic liver diseases.

Authors+Show Affiliations

Health and Sciences Department, Biological and Health Sciences Division, Metropolitan Independent University, México, DF, México.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20594261

Citation

González-Puertos, Viridiana Y., et al. "Bcl-2 Overexpression in Hepatic Stellate Cell Line CFSC-2G, Induces a Pro-fibrotic State." Journal of Gastroenterology and Hepatology, vol. 25, no. 7, 2010, pp. 1306-14.
González-Puertos VY, Hernández-Pérez E, Nuño-Lámbarri N, et al. Bcl-2 overexpression in hepatic stellate cell line CFSC-2G, induces a pro-fibrotic state. J Gastroenterol Hepatol. 2010;25(7):1306-14.
González-Puertos, V. Y., Hernández-Pérez, E., Nuño-Lámbarri, N., Ventura-Gallegos, J. L., López-Diázguerrero, N. E., Robles-Díaz, G., Gutiérrez-Ruiz, M. C., & Konigsberg, M. (2010). Bcl-2 overexpression in hepatic stellate cell line CFSC-2G, induces a pro-fibrotic state. Journal of Gastroenterology and Hepatology, 25(7), 1306-14. https://doi.org/10.1111/j.1440-1746.2009.06175.x
González-Puertos VY, et al. Bcl-2 Overexpression in Hepatic Stellate Cell Line CFSC-2G, Induces a Pro-fibrotic State. J Gastroenterol Hepatol. 2010;25(7):1306-14. PubMed PMID: 20594261.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Bcl-2 overexpression in hepatic stellate cell line CFSC-2G, induces a pro-fibrotic state. AU - González-Puertos,Viridiana Y, AU - Hernández-Pérez,Elizabeth, AU - Nuño-Lámbarri,Natalia, AU - Ventura-Gallegos,José L, AU - López-Diázguerrero,Norma E, AU - Robles-Díaz,Guillermo, AU - Gutiérrez-Ruiz,María C, AU - Konigsberg,Mina, PY - 2010/7/3/entrez PY - 2010/7/3/pubmed PY - 2010/10/19/medline SP - 1306 EP - 14 JF - Journal of gastroenterology and hepatology JO - J Gastroenterol Hepatol VL - 25 IS - 7 N2 - BACKGROUND AND AIM: Development of hepatic fibrosis is a complex process that involves oxidative stress (OS) and an altered balance between pro- and anti-apoptotic molecules. Since Bcl-2 overexpression preserves viability against OS, our objective was to address the effect of Bcl-2 overexpression in the hepatic stellate cells (HSC) cell-line CFSC-2G under acetaldehyde and H(2)O(2) challenge, and explore if it protects these cells against OS, induces replicative senescence and/or modify extracellular matrix (ECM) remodeling potential. METHODS: To induce Bcl-2 overexpression, HSC cell line CFSC-2G was transfected by lipofection technique. Green fluorescent protein-only CFSC-2G cells were used as a control. Cell survival after H(2)O(2) treatment and total protein oxidation were assessed. To determine cell cycle arrest, proliferation-rate, DNA synthesis and senescence were assessed. Matrix metalloproteinases (MMP), tissue-inhibitor of MMP (TIMP), transglutaminases (TG) and smooth muscle a-actin (alpha-SMA) were evaluated by western blot in response to acetaldehyde treatment as markers of ECM remodeling capacity in addition to transforming growth factor-beta (TGF-beta) mRNA. RESULTS: Cells overexpressing Bcl-2 survived approximately 20% more than control cells when exposed to H(2)O(2) and approximately 35% proteins were protected from oxidation, but Bcl-2 did not slow proliferation or induced senescence. Bcl-2 overexpression did not change alpha-SMA levels, but it increased TIMP-1 (55%), tissue transglutaminases (tTG) (25%) and TGF-beta mRNA (49%), when exposed to acetaldehyde, while MMP-13 content decreased (47%). CONCLUSIONS: Bcl-2 overexpression protected HSC against oxidative stress but it did not induce replicative senescence. It increased TIMP-1, tTG and TGF-beta mRNA levels and decreased MMP-13 content, suggesting that Bcl-2 overexpression may play a key role in the progression of fibrosis in chronic liver diseases. SN - 1440-1746 UR - https://www.unboundmedicine.com/medline/citation/20594261/Bcl_2_overexpression_in_hepatic_stellate_cell_line_CFSC_2G_induces_a_pro_fibrotic_state_ L2 - https://doi.org/10.1111/j.1440-1746.2009.06175.x DB - PRIME DP - Unbound Medicine ER -