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Matrix Conditions and KLF2-Dependent Induction of Heme Oxygenase-1 Modulate Inhibition of HCV Replication by Fluvastatin

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Matrix Conditions and KLF2-Dependent Induction of Heme Oxygenase-1 Modulate Inhibition of HCV Replication by Fluvastatin. / Wüstenberg, Andrea; Kah, Janine; Singethan, Katrin; Sirma, Hüseyin; Keller, Amelie Dorothea; Perez Rosal, Sergio René; Schrader, Jörg; Loscher, Christine; Volz, Tassilo; Bartenschlager, Ralf; Lohmann, Volker; Protzer, Ulrike; Dandri, Maura; Lohse, Ansgar W; Tiegs, Gisa; Sass, Gabriele.

In: PLOS ONE, Vol. 9, No. 5, 01.01.2014, p. e96533.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Wüstenberg, A, Kah, J, Singethan, K, Sirma, H, Keller, AD, Perez Rosal, SR, Schrader, J, Loscher, C, Volz, T, Bartenschlager, R, Lohmann, V, Protzer, U, Dandri, M, Lohse, AW, Tiegs, G & Sass, G 2014, 'Matrix Conditions and KLF2-Dependent Induction of Heme Oxygenase-1 Modulate Inhibition of HCV Replication by Fluvastatin', PLOS ONE, vol. 9, no. 5, pp. e96533. https://doi.org/10.1371/journal.pone.0096533

APA

Wüstenberg, A., Kah, J., Singethan, K., Sirma, H., Keller, A. D., Perez Rosal, S. R., Schrader, J., Loscher, C., Volz, T., Bartenschlager, R., Lohmann, V., Protzer, U., Dandri, M., Lohse, A. W., Tiegs, G., & Sass, G. (2014). Matrix Conditions and KLF2-Dependent Induction of Heme Oxygenase-1 Modulate Inhibition of HCV Replication by Fluvastatin. PLOS ONE, 9(5), e96533. https://doi.org/10.1371/journal.pone.0096533

Vancouver

Wüstenberg A, Kah J, Singethan K, Sirma H, Keller AD, Perez Rosal SR et al. Matrix Conditions and KLF2-Dependent Induction of Heme Oxygenase-1 Modulate Inhibition of HCV Replication by Fluvastatin. PLOS ONE. 2014 Jan 1;9(5):e96533. https://doi.org/10.1371/journal.pone.0096533

Bibtex

@article{188c260126ac46f4a0c757813e8e0095,
title = "Matrix Conditions and KLF2-Dependent Induction of Heme Oxygenase-1 Modulate Inhibition of HCV Replication by Fluvastatin",
abstract = "BACKGROUND & AIMS: HMG-CoA-reductase-inhibitors (statins) have been shown to interfere with HCV replication in vitro. We investigated the mechanism, requirements and contribution of heme oxygenase-1(HO-1)-induction by statins to interference with HCV replication.METHODS: HO-1-induction by fluva-, simva-, rosuva-, atorva- or pravastatin was correlated to HCV replication, using non-infectious replicon systems as well as the infectious cell culture system. The mechanism of HO-1-induction by statins as well as its relevance for interference with HCV replication was investigated using transient or permanent knockdown cell lines. Polyacrylamide(PAA) gels of different density degrees or the Rho-kinase-inhibitor Hydroxyfasudil were used in order to mimic matrix conditions corresponding to normal versus fibrotic liver tissue.RESULTS: All statins used, except pravastatin, decreased HCV replication and induced HO-1 expression, as well as interferon response in vitro. HO-1-induction was mediated by reduction of Bach1 expression and induction of the Nuclear factor (erythroid-derived 2)-like 2 (NRF2) cofactor Krueppel-like factor 2 (KLF2). Knockdown of KLF2 or HO-1 abrogated effects of statins on HCV replication. HO-1-induction and anti-viral effects of statins were more pronounced under cell culture conditions mimicking advanced stages of liver disease.CONCLUSIONS: Statin-mediated effects on HCV replication seem to require HO-1-induction, which is more pronounced in a microenvironment resembling fibrotic liver tissue. This implicates that certain statins might be especially useful to support HCV therapy of patients at advanced stages of liver disease.",
author = "Andrea W{\"u}stenberg and Janine Kah and Katrin Singethan and H{\"u}seyin Sirma and Keller, {Amelie Dorothea} and {Perez Rosal}, {Sergio Ren{\'e}} and J{\"o}rg Schrader and Christine Loscher and Tassilo Volz and Ralf Bartenschlager and Volker Lohmann and Ulrike Protzer and Maura Dandri and Lohse, {Ansgar W} and Gisa Tiegs and Gabriele Sass",
year = "2014",
month = jan,
day = "1",
doi = "10.1371/journal.pone.0096533",
language = "English",
volume = "9",
pages = "e96533",
journal = "PLOS ONE",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "5",

}

RIS

TY - JOUR

T1 - Matrix Conditions and KLF2-Dependent Induction of Heme Oxygenase-1 Modulate Inhibition of HCV Replication by Fluvastatin

AU - Wüstenberg, Andrea

AU - Kah, Janine

AU - Singethan, Katrin

AU - Sirma, Hüseyin

AU - Keller, Amelie Dorothea

AU - Perez Rosal, Sergio René

AU - Schrader, Jörg

AU - Loscher, Christine

AU - Volz, Tassilo

AU - Bartenschlager, Ralf

AU - Lohmann, Volker

AU - Protzer, Ulrike

AU - Dandri, Maura

AU - Lohse, Ansgar W

AU - Tiegs, Gisa

AU - Sass, Gabriele

PY - 2014/1/1

Y1 - 2014/1/1

N2 - BACKGROUND & AIMS: HMG-CoA-reductase-inhibitors (statins) have been shown to interfere with HCV replication in vitro. We investigated the mechanism, requirements and contribution of heme oxygenase-1(HO-1)-induction by statins to interference with HCV replication.METHODS: HO-1-induction by fluva-, simva-, rosuva-, atorva- or pravastatin was correlated to HCV replication, using non-infectious replicon systems as well as the infectious cell culture system. The mechanism of HO-1-induction by statins as well as its relevance for interference with HCV replication was investigated using transient or permanent knockdown cell lines. Polyacrylamide(PAA) gels of different density degrees or the Rho-kinase-inhibitor Hydroxyfasudil were used in order to mimic matrix conditions corresponding to normal versus fibrotic liver tissue.RESULTS: All statins used, except pravastatin, decreased HCV replication and induced HO-1 expression, as well as interferon response in vitro. HO-1-induction was mediated by reduction of Bach1 expression and induction of the Nuclear factor (erythroid-derived 2)-like 2 (NRF2) cofactor Krueppel-like factor 2 (KLF2). Knockdown of KLF2 or HO-1 abrogated effects of statins on HCV replication. HO-1-induction and anti-viral effects of statins were more pronounced under cell culture conditions mimicking advanced stages of liver disease.CONCLUSIONS: Statin-mediated effects on HCV replication seem to require HO-1-induction, which is more pronounced in a microenvironment resembling fibrotic liver tissue. This implicates that certain statins might be especially useful to support HCV therapy of patients at advanced stages of liver disease.

AB - BACKGROUND & AIMS: HMG-CoA-reductase-inhibitors (statins) have been shown to interfere with HCV replication in vitro. We investigated the mechanism, requirements and contribution of heme oxygenase-1(HO-1)-induction by statins to interference with HCV replication.METHODS: HO-1-induction by fluva-, simva-, rosuva-, atorva- or pravastatin was correlated to HCV replication, using non-infectious replicon systems as well as the infectious cell culture system. The mechanism of HO-1-induction by statins as well as its relevance for interference with HCV replication was investigated using transient or permanent knockdown cell lines. Polyacrylamide(PAA) gels of different density degrees or the Rho-kinase-inhibitor Hydroxyfasudil were used in order to mimic matrix conditions corresponding to normal versus fibrotic liver tissue.RESULTS: All statins used, except pravastatin, decreased HCV replication and induced HO-1 expression, as well as interferon response in vitro. HO-1-induction was mediated by reduction of Bach1 expression and induction of the Nuclear factor (erythroid-derived 2)-like 2 (NRF2) cofactor Krueppel-like factor 2 (KLF2). Knockdown of KLF2 or HO-1 abrogated effects of statins on HCV replication. HO-1-induction and anti-viral effects of statins were more pronounced under cell culture conditions mimicking advanced stages of liver disease.CONCLUSIONS: Statin-mediated effects on HCV replication seem to require HO-1-induction, which is more pronounced in a microenvironment resembling fibrotic liver tissue. This implicates that certain statins might be especially useful to support HCV therapy of patients at advanced stages of liver disease.

U2 - 10.1371/journal.pone.0096533

DO - 10.1371/journal.pone.0096533

M3 - SCORING: Journal article

C2 - 24801208

VL - 9

SP - e96533

JO - PLOS ONE

JF - PLOS ONE

SN - 1932-6203

IS - 5

ER -