Publication

Kruppel-like factor 6 is a transcriptional activator of autophagy in acute liver injury

Sydor, S., Manka, P., Best, J., Jafoui, S., Sowa, J-P., Zoubek, M. E., Hernandez-Gea, V., Cubero, F. J., Kälsch, J., Vetter, D., Fiel, M. I., Hoshida, Y., Bian, C. B., Nelson, L. J., Moshage, H., Faber, K. N., Paul, A., Baba, H. A., Gerken, G., Friedman, S. L., Canbay, A. & Bechmann, L. P. 14-Aug-2017 In : Scientific Reports. 7, 1, 12 p., 8119

Research output: Scientific - peer-reviewArticle

APA

Sydor, S., Manka, P., Best, J., Jafoui, S., Sowa, J-P., Zoubek, M. E., ... Bechmann, L. P. (2017). Kruppel-like factor 6 is a transcriptional activator of autophagy in acute liver injury. Scientific Reports, 7(1), [8119]. DOI: 10.1038/s41598-017-08680-w

Author

Sydor, Svenja; Manka, Paul; Best, Jan; Jafoui, Sami; Sowa, Jan-Peter; Zoubek, Miguel Eugenio; Hernandez-Gea, Virginia; Cubero, Francisco Javier; Kälsch, Julia; Vetter, Diana; Fiel, Maria Isabel; Hoshida, Yujin; Bian, C Billie; Nelson, Leonard J; Moshage, Han; Faber, Klaas Nico; Paul, Andreas; Baba, Hideo A; Gerken, Guido; Friedman, Scott L; Canbay, Ali; Bechmann, Lars P / Kruppel-like factor 6 is a transcriptional activator of autophagy in acute liver injury.

In: Scientific Reports, Vol. 7, No. 1, 8119, 14.08.2017.

Research output: Scientific - peer-reviewArticle

Harvard

Sydor, S, Manka, P, Best, J, Jafoui, S, Sowa, J-P, Zoubek, ME, Hernandez-Gea, V, Cubero, FJ, Kälsch, J, Vetter, D, Fiel, MI, Hoshida, Y, Bian, CB, Nelson, LJ, Moshage, H, Faber, KN, Paul, A, Baba, HA, Gerken, G, Friedman, SL, Canbay, A & Bechmann, LP 2017, 'Kruppel-like factor 6 is a transcriptional activator of autophagy in acute liver injury' Scientific Reports, vol 7, no. 1, 8119. DOI: 10.1038/s41598-017-08680-w

Standard

Kruppel-like factor 6 is a transcriptional activator of autophagy in acute liver injury. / Sydor, Svenja; Manka, Paul; Best, Jan; Jafoui, Sami; Sowa, Jan-Peter; Zoubek, Miguel Eugenio; Hernandez-Gea, Virginia; Cubero, Francisco Javier; Kälsch, Julia; Vetter, Diana; Fiel, Maria Isabel; Hoshida, Yujin; Bian, C Billie; Nelson, Leonard J; Moshage, Han; Faber, Klaas Nico; Paul, Andreas; Baba, Hideo A; Gerken, Guido; Friedman, Scott L; Canbay, Ali; Bechmann, Lars P.

In: Scientific Reports, Vol. 7, No. 1, 8119, 14.08.2017.

Research output: Scientific - peer-reviewArticle

Vancouver

Sydor S, Manka P, Best J, Jafoui S, Sowa J-P, Zoubek ME et al. Kruppel-like factor 6 is a transcriptional activator of autophagy in acute liver injury. Scientific Reports. 2017 Aug 14;7(1). 8119. Available from, DOI: 10.1038/s41598-017-08680-w


BibTeX

@article{1f5a1dacaacd423c854e6222d3f65753,
title = "Kruppel-like factor 6 is a transcriptional activator of autophagy in acute liver injury",
abstract = "Kruppel-like factor 6 (KLF6) is a transcription factor and tumor suppressor. We previously identified KLF6 as mediator of hepatocyte glucose and lipid homeostasis. The loss or reduction of KLF6 is linked to the progression of hepatocellular carcinoma, but its contribution to liver regeneration and repair in acute liver injury are lacking so far. Here we explore the role of KLF6 in acute liver injury models in mice, and in patients with acute liver failure (ALF). KLF6 was induced in hepatocytes in ALF, and in both acetaminophen (APAP)- and carbon tetrachloride (CCl4)- treated mice. In mice with hepatocytespecific Klf6 knockout (DeltaKlf6), cell proliferation following partial hepatectomy (PHx) was increased compared to controls. Interestingly, key autophagic markers and mediators LC3-II, Atg7 and Beclin1 were reduced in DeltaKlf6 mice livers. Using luciferase assay and ChIP, KLF6 was established as a direct transcriptional activator of ATG7 and BECLIN1, but was dependent on the presence of p53. Here we show, that KLF6 expression is induced in ALF and in the regenerating liver, where it activates autophagy by transcriptional induction of ATG7 and BECLIN1 in a p53-dependent manner. These findings couple the activity of an important growth inhibitor in liver to the induction of autophagy in hepatocytes.",
keywords = "KLF6 TUMOR-SUPPRESSOR, HUMAN HEPATOCELLULAR-CARCINOMA, PARTIAL-HEPATECTOMY, DOWN-REGULATION, IN-VIVO, PROTEIN, GROWTH, MICE, P53, REGENERATION",
author = "Svenja Sydor and Paul Manka and Jan Best and Sami Jafoui and Jan-Peter Sowa and Zoubek, {Miguel Eugenio} and Virginia Hernandez-Gea and Cubero, {Francisco Javier} and Julia Kälsch and Diana Vetter and Fiel, {Maria Isabel} and Yujin Hoshida and Bian, {C Billie} and Nelson, {Leonard J} and Han Moshage and Faber, {Klaas Nico} and Andreas Paul and Baba, {Hideo A} and Guido Gerken and Friedman, {Scott L} and Ali Canbay and Bechmann, {Lars P}",
year = "2017",
month = "8",
doi = "10.1038/s41598-017-08680-w",
volume = "7",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",

}

RIS

TY - JOUR

T1 - Kruppel-like factor 6 is a transcriptional activator of autophagy in acute liver injury

AU - Sydor,Svenja

AU - Manka,Paul

AU - Best,Jan

AU - Jafoui,Sami

AU - Sowa,Jan-Peter

AU - Zoubek,Miguel Eugenio

AU - Hernandez-Gea,Virginia

AU - Cubero,Francisco Javier

AU - Kälsch,Julia

AU - Vetter,Diana

AU - Fiel,Maria Isabel

AU - Hoshida,Yujin

AU - Bian,C Billie

AU - Nelson,Leonard J

AU - Moshage,Han

AU - Faber,Klaas Nico

AU - Paul,Andreas

AU - Baba,Hideo A

AU - Gerken,Guido

AU - Friedman,Scott L

AU - Canbay,Ali

AU - Bechmann,Lars P

PY - 2017/8/14

Y1 - 2017/8/14

N2 - Kruppel-like factor 6 (KLF6) is a transcription factor and tumor suppressor. We previously identified KLF6 as mediator of hepatocyte glucose and lipid homeostasis. The loss or reduction of KLF6 is linked to the progression of hepatocellular carcinoma, but its contribution to liver regeneration and repair in acute liver injury are lacking so far. Here we explore the role of KLF6 in acute liver injury models in mice, and in patients with acute liver failure (ALF). KLF6 was induced in hepatocytes in ALF, and in both acetaminophen (APAP)- and carbon tetrachloride (CCl4)- treated mice. In mice with hepatocytespecific Klf6 knockout (DeltaKlf6), cell proliferation following partial hepatectomy (PHx) was increased compared to controls. Interestingly, key autophagic markers and mediators LC3-II, Atg7 and Beclin1 were reduced in DeltaKlf6 mice livers. Using luciferase assay and ChIP, KLF6 was established as a direct transcriptional activator of ATG7 and BECLIN1, but was dependent on the presence of p53. Here we show, that KLF6 expression is induced in ALF and in the regenerating liver, where it activates autophagy by transcriptional induction of ATG7 and BECLIN1 in a p53-dependent manner. These findings couple the activity of an important growth inhibitor in liver to the induction of autophagy in hepatocytes.

AB - Kruppel-like factor 6 (KLF6) is a transcription factor and tumor suppressor. We previously identified KLF6 as mediator of hepatocyte glucose and lipid homeostasis. The loss or reduction of KLF6 is linked to the progression of hepatocellular carcinoma, but its contribution to liver regeneration and repair in acute liver injury are lacking so far. Here we explore the role of KLF6 in acute liver injury models in mice, and in patients with acute liver failure (ALF). KLF6 was induced in hepatocytes in ALF, and in both acetaminophen (APAP)- and carbon tetrachloride (CCl4)- treated mice. In mice with hepatocytespecific Klf6 knockout (DeltaKlf6), cell proliferation following partial hepatectomy (PHx) was increased compared to controls. Interestingly, key autophagic markers and mediators LC3-II, Atg7 and Beclin1 were reduced in DeltaKlf6 mice livers. Using luciferase assay and ChIP, KLF6 was established as a direct transcriptional activator of ATG7 and BECLIN1, but was dependent on the presence of p53. Here we show, that KLF6 expression is induced in ALF and in the regenerating liver, where it activates autophagy by transcriptional induction of ATG7 and BECLIN1 in a p53-dependent manner. These findings couple the activity of an important growth inhibitor in liver to the induction of autophagy in hepatocytes.

KW - KLF6 TUMOR-SUPPRESSOR

KW - HUMAN HEPATOCELLULAR-CARCINOMA

KW - PARTIAL-HEPATECTOMY

KW - DOWN-REGULATION

KW - IN-VIVO

KW - PROTEIN

KW - GROWTH

KW - MICE

KW - P53

KW - REGENERATION

U2 - 10.1038/s41598-017-08680-w

DO - 10.1038/s41598-017-08680-w

M3 - Article

VL - 7

JO - Scientific Reports

T2 - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 1

M1 - 8119

ER -

ID: 46961963