GDF15 deficiency exacerbates chronic alcohol- and carbon tetrachloride-induced liver injury (2024)

Chung, H. K., Kim, J. T., Kim, H. W., Kwon, M., Kim, S. Y., Shong, M., Kim, K. S., & Yi, H. S. (2017). GDF15 deficiency exacerbates chronic alcohol- and carbon tetrachloride-induced liver injury. Scientific Reports, 7(1), Article 17238. https://doi.org/10.1038/s41598-017-17574-w

Chung, Hyo Kyun ; Kim, Jung Tae ; Kim, Hyeon Woo et al. / GDF15 deficiency exacerbates chronic alcohol- and carbon tetrachloride-induced liver injury. In: Scientific Reports. 2017 ; Vol. 7, No. 1.

@article{b475d1e8368c4ab48f870838a0b0c3ea,

title = "GDF15 deficiency exacerbates chronic alcohol- and carbon tetrachloride-induced liver injury",

abstract = "Growth differentiation factor 15 (GDF15) has recently been shown to have an important role in the regulation of mitochondrial function and in the pathogenesis of complex human diseases. Nevertheless, the role of GDF15 in alcohol-induced or fibrotic liver diseases has yet to be determined. In this study, we demonstrate that alcohol- or carbon tetrachloride (CCl4)-mediated hepatic GDF15 production ameliorates liver inflammation and fibrosis. Alcohol directly enhanced GDF15 expression in primary hepatocytes, which led to increased oxygen consumption. Moreover, GDF15 reduced the expression of pro-inflammatory cytokines in liver-resident macrophages, leading to an improvement in inflammation and fibrosis in the liver. GDF15 knockout (KO) mice had more TNF-α-producing T cells and more activated CD4+ and CD8+ T cells in the liver than wild-type mice. Liver-infiltrating monocytes and neutrophils were also increased in the GDF15 KO mice during liver fibrogenesis. These changes in hepatic immune cells were associated with increased tissue inflammation and fibrosis. Finally, recombinant GDF15 decreased the expression of pro-inflammatory cytokines and fibrotic mediators and prevented the activation of T cells in the livers of mice with CCl4-induced liver fibrosis. These results suggest that GDF15 could be a potential therapeutic target for the treatment of alcohol-induced and fibrotic liver diseases.",

author = "Chung, {Hyo Kyun} and Kim, {Jung Tae} and Kim, {Hyeon Woo} and Minjoo Kwon and Kim, {So Yeon} and Minho Shong and Kim, {Koon Soon} and Yi, {Hyon Seung}",

note = "Publisher Copyright: {\textcopyright} 2017 The Author(s).",

year = "2017",

month = dec,

day = "1",

doi = "10.1038/s41598-017-17574-w",

language = "English",

volume = "7",

journal = "Scientific Reports",

issn = "2045-2322",

number = "1",

}

Chung, HK, Kim, JT, Kim, HW, Kwon, M, Kim, SY, Shong, M, Kim, KS & Yi, HS 2017, 'GDF15 deficiency exacerbates chronic alcohol- and carbon tetrachloride-induced liver injury', Scientific Reports, vol. 7, no. 1, 17238. https://doi.org/10.1038/s41598-017-17574-w

GDF15 deficiency exacerbates chronic alcohol- and carbon tetrachloride-induced liver injury. / Chung, Hyo Kyun; Kim, Jung Tae; Kim, Hyeon Woo et al.
In: Scientific Reports, Vol. 7, No. 1, 17238, 01.12.2017.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - GDF15 deficiency exacerbates chronic alcohol- and carbon tetrachloride-induced liver injury

AU - Chung, Hyo Kyun

AU - Kim, Jung Tae

AU - Kim, Hyeon Woo

AU - Kwon, Minjoo

AU - Kim, So Yeon

AU - Shong, Minho

AU - Kim, Koon Soon

AU - Yi, Hyon Seung

N1 - Publisher Copyright:© 2017 The Author(s).

PY - 2017/12/1

Y1 - 2017/12/1

N2 - Growth differentiation factor 15 (GDF15) has recently been shown to have an important role in the regulation of mitochondrial function and in the pathogenesis of complex human diseases. Nevertheless, the role of GDF15 in alcohol-induced or fibrotic liver diseases has yet to be determined. In this study, we demonstrate that alcohol- or carbon tetrachloride (CCl4)-mediated hepatic GDF15 production ameliorates liver inflammation and fibrosis. Alcohol directly enhanced GDF15 expression in primary hepatocytes, which led to increased oxygen consumption. Moreover, GDF15 reduced the expression of pro-inflammatory cytokines in liver-resident macrophages, leading to an improvement in inflammation and fibrosis in the liver. GDF15 knockout (KO) mice had more TNF-α-producing T cells and more activated CD4+ and CD8+ T cells in the liver than wild-type mice. Liver-infiltrating monocytes and neutrophils were also increased in the GDF15 KO mice during liver fibrogenesis. These changes in hepatic immune cells were associated with increased tissue inflammation and fibrosis. Finally, recombinant GDF15 decreased the expression of pro-inflammatory cytokines and fibrotic mediators and prevented the activation of T cells in the livers of mice with CCl4-induced liver fibrosis. These results suggest that GDF15 could be a potential therapeutic target for the treatment of alcohol-induced and fibrotic liver diseases.

AB - Growth differentiation factor 15 (GDF15) has recently been shown to have an important role in the regulation of mitochondrial function and in the pathogenesis of complex human diseases. Nevertheless, the role of GDF15 in alcohol-induced or fibrotic liver diseases has yet to be determined. In this study, we demonstrate that alcohol- or carbon tetrachloride (CCl4)-mediated hepatic GDF15 production ameliorates liver inflammation and fibrosis. Alcohol directly enhanced GDF15 expression in primary hepatocytes, which led to increased oxygen consumption. Moreover, GDF15 reduced the expression of pro-inflammatory cytokines in liver-resident macrophages, leading to an improvement in inflammation and fibrosis in the liver. GDF15 knockout (KO) mice had more TNF-α-producing T cells and more activated CD4+ and CD8+ T cells in the liver than wild-type mice. Liver-infiltrating monocytes and neutrophils were also increased in the GDF15 KO mice during liver fibrogenesis. These changes in hepatic immune cells were associated with increased tissue inflammation and fibrosis. Finally, recombinant GDF15 decreased the expression of pro-inflammatory cytokines and fibrotic mediators and prevented the activation of T cells in the livers of mice with CCl4-induced liver fibrosis. These results suggest that GDF15 could be a potential therapeutic target for the treatment of alcohol-induced and fibrotic liver diseases.

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U2 - 10.1038/s41598-017-17574-w

DO - 10.1038/s41598-017-17574-w

M3 - Article

C2 - 29222479

AN - SCOPUS:85042395857

SN - 2045-2322

VL - 7

JO - Scientific Reports

JF - Scientific Reports

IS - 1

M1 - 17238

ER -

Chung HK, Kim JT, Kim HW, Kwon M, Kim SY, Shong M et al. GDF15 deficiency exacerbates chronic alcohol- and carbon tetrachloride-induced liver injury. Scientific Reports. 2017 Dec 1;7(1):17238. doi: 10.1038/s41598-017-17574-w