Granulocyte colony stimulating factor treatment in non-alcoholic fatty liver disease: beyond marrow cell mobilization
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Ho Hyun Nam1, Dae Won Jun2,*, Kiseok Jang3,*, Waqar Khalid Saeed2, Jai Sun Lee1, Hyeon Tae Kang1 and Yeon Ji Chae1
1Department of Translational Medicine, Hanyang University Graduate School of Biomedical Science and Engineering, Seoul, South Korea
2Department Internal Medicine, Hanyang University School of Medicine, Seoul, South Korea
3Department of Pathology, Hanyang University School of Medicine, Seoul, South Korea
*These authors contributed equally to this work
Dae Won Jun, email: firstname.lastname@example.org
Kiseok Jang, email: email@example.com
Keywords: non-alcoholic fatty liver, granulocyte colony stimulating factor, apoptosis
Received: December 10, 2016 Accepted: June 18, 2017 Published: July 04, 2017
Protective effects of granulocyte colony stimulating factor (G-CSF) in acute liver injury via marrow cell mobilization have been reported in several studies. But exact mode of action and optimal protocol of G-CSF has been still doubt in chronic disease. Here we investigated mode of action and optimization of G-CSF as a treatment for non-alcoholic fatty liver disease (NAFLD). Various doses of conventional G-CSF (30 μg/kg once weekly, once daily for 5 days, twice weekly) and long acting G-CSF (30 μg/kg once a month) were evaluated in two kinds of NAFLD animal models to optimize the G-CSF protocol. G-CSF receptor expression highest increased in NAFLD model among various liver diseases compare to control (NAFLD: 14.7 times, alcohol hepatitis: 7.1 times, cirrhosis: 2.4 times, and ischemia reperfusion: 6.8 times). G-CSF treatment reduced intrahepatic fat accumulation, and inflammation in two kinds of NAFLD animal models. G-CSF increased PI3K/Akt expression in hepatocyte as well as decreased apoptotic drive (increased Bcl-2 expression and decreased Bax expression) in animal model. Five day consecutive G-CSF treatment and once a month long acting G-CSF increased marrow derived stem cell marker in peripheral blood. But twice a week conventional G-CSF treatment did not increased CD34+ cell in peripheral blood and liver neither. Not only high dose G-CSF (once daily for 5 days) but also hepatotropic dose G-CSF (twice a week) significantly reduced hepatocyte apoptosis via PI3K and Akt pathway activation without marrow cell mobilization in NAFLD animal model.
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