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A new histone deacetylase inhibitor improves liver fibrosis in BDL rats through suppression of hepatic stellate cells.

Park KC, Park JH, Jeon JY, Kim SY, Kim JM, Lim CY, Lee TH, Kim HK, Lee HG, Kim SM, Kwon HJ, Suh JS, Kim SW, Choi SH - Br. J. Pharmacol. (2014)

Bottom Line: In addition, HNHA induced apoptosis of HSCs, which was correlated with reduced COX-2 expression, NF-κB activation and cell death signals.HNHA restored liver function and decreased the accumulation of extracellular matrix in the liver via suppression of HSC activation in BDL rats in vivo.HNHA improved liver function, suppressed liver fibrosis and increased survival of BDL rats, accompanied by reduction of cell growth, activation and survival of HSCs.

View Article: PubMed Central - PubMed

Affiliation: Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea; Department of Surgery, Yonsei University College of Medicine, Seoul, Korea.

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Effects of HNHA on proliferation, apoptosis and activation of HSCs. (A, B) Cell growth assay of mouse (A) or human (B) primary HSCs using cell counting. (C) Western blot analysis of HSC activation markers in mouse HSCs. (D) Cell cycle phase distribution by flow cytometric DNA in mouse HSCs. (E) Western blot analysis of cell proliferation protein levels in activated mouse HSCs. (F) Quantitative RT-PCR analysis of p21 in activated mouse HSCs. Mouse primary HSCs were cultured in complete media with increasing concentrations of drugs for 48 h. (G) Cell viability assay. Mouse primary HSCs were cultured in complete media with increasing concentrations of drugs for 96 h (n = 3). (H) Western blot analysis of apoptosis-related proteins and HDAC levels in mouse HSCs. In the experiments summarized in (C)–(F) and in (H), mouse HSCs were incubated with ibuprofen, meloxicam, SAHA or HNHA at a final concentration of 10 μM. Data shown are means ± SD (n = 4 except for G). *P < 0.05, **P < 0.01, ***P < 0.005 versus control or ibuprofen.
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fig01: Effects of HNHA on proliferation, apoptosis and activation of HSCs. (A, B) Cell growth assay of mouse (A) or human (B) primary HSCs using cell counting. (C) Western blot analysis of HSC activation markers in mouse HSCs. (D) Cell cycle phase distribution by flow cytometric DNA in mouse HSCs. (E) Western blot analysis of cell proliferation protein levels in activated mouse HSCs. (F) Quantitative RT-PCR analysis of p21 in activated mouse HSCs. Mouse primary HSCs were cultured in complete media with increasing concentrations of drugs for 48 h. (G) Cell viability assay. Mouse primary HSCs were cultured in complete media with increasing concentrations of drugs for 96 h (n = 3). (H) Western blot analysis of apoptosis-related proteins and HDAC levels in mouse HSCs. In the experiments summarized in (C)–(F) and in (H), mouse HSCs were incubated with ibuprofen, meloxicam, SAHA or HNHA at a final concentration of 10 μM. Data shown are means ± SD (n = 4 except for G). *P < 0.05, **P < 0.01, ***P < 0.005 versus control or ibuprofen.

Mentions: HNHA treatment for 1 week showed greater inhibition of mouse and human primary HSC proliferation, a feature of HSC activation, compared with ibuprofen (a non-selective COX inhibitor), meloxicam (a COX-2 selective inhibitor) and SAHA (another HDAC inhibitor) (Figure 1A and B).


A new histone deacetylase inhibitor improves liver fibrosis in BDL rats through suppression of hepatic stellate cells.

Park KC, Park JH, Jeon JY, Kim SY, Kim JM, Lim CY, Lee TH, Kim HK, Lee HG, Kim SM, Kwon HJ, Suh JS, Kim SW, Choi SH - Br. J. Pharmacol. (2014)

Effects of HNHA on proliferation, apoptosis and activation of HSCs. (A, B) Cell growth assay of mouse (A) or human (B) primary HSCs using cell counting. (C) Western blot analysis of HSC activation markers in mouse HSCs. (D) Cell cycle phase distribution by flow cytometric DNA in mouse HSCs. (E) Western blot analysis of cell proliferation protein levels in activated mouse HSCs. (F) Quantitative RT-PCR analysis of p21 in activated mouse HSCs. Mouse primary HSCs were cultured in complete media with increasing concentrations of drugs for 48 h. (G) Cell viability assay. Mouse primary HSCs were cultured in complete media with increasing concentrations of drugs for 96 h (n = 3). (H) Western blot analysis of apoptosis-related proteins and HDAC levels in mouse HSCs. In the experiments summarized in (C)–(F) and in (H), mouse HSCs were incubated with ibuprofen, meloxicam, SAHA or HNHA at a final concentration of 10 μM. Data shown are means ± SD (n = 4 except for G). *P < 0.05, **P < 0.01, ***P < 0.005 versus control or ibuprofen.
© Copyright Policy - open-access
Related In: Results  -  Collection

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fig01: Effects of HNHA on proliferation, apoptosis and activation of HSCs. (A, B) Cell growth assay of mouse (A) or human (B) primary HSCs using cell counting. (C) Western blot analysis of HSC activation markers in mouse HSCs. (D) Cell cycle phase distribution by flow cytometric DNA in mouse HSCs. (E) Western blot analysis of cell proliferation protein levels in activated mouse HSCs. (F) Quantitative RT-PCR analysis of p21 in activated mouse HSCs. Mouse primary HSCs were cultured in complete media with increasing concentrations of drugs for 48 h. (G) Cell viability assay. Mouse primary HSCs were cultured in complete media with increasing concentrations of drugs for 96 h (n = 3). (H) Western blot analysis of apoptosis-related proteins and HDAC levels in mouse HSCs. In the experiments summarized in (C)–(F) and in (H), mouse HSCs were incubated with ibuprofen, meloxicam, SAHA or HNHA at a final concentration of 10 μM. Data shown are means ± SD (n = 4 except for G). *P < 0.05, **P < 0.01, ***P < 0.005 versus control or ibuprofen.
Mentions: HNHA treatment for 1 week showed greater inhibition of mouse and human primary HSC proliferation, a feature of HSC activation, compared with ibuprofen (a non-selective COX inhibitor), meloxicam (a COX-2 selective inhibitor) and SAHA (another HDAC inhibitor) (Figure 1A and B).

Bottom Line: In addition, HNHA induced apoptosis of HSCs, which was correlated with reduced COX-2 expression, NF-κB activation and cell death signals.HNHA restored liver function and decreased the accumulation of extracellular matrix in the liver via suppression of HSC activation in BDL rats in vivo.HNHA improved liver function, suppressed liver fibrosis and increased survival of BDL rats, accompanied by reduction of cell growth, activation and survival of HSCs.

View Article: PubMed Central - PubMed

Affiliation: Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea; Department of Surgery, Yonsei University College of Medicine, Seoul, Korea.

Show MeSH
Related in: MedlinePlus