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

Cited 25 time in webofscience Cited 0 time in scopus
  • Hit : 173
  • Download : 280
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-alpha-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.
Publisher
NATURE PUBLISHING GROUP
Issue Date
2017-12
Language
English
Article Type
Article
Keywords

HEPATIC MITOCHONDRIAL-DNA; NONALCOHOLIC STEATOHEPATITIS; STELLATE CELLS; MOUSE-LIVER; MICE; FIBROSIS; ETHANOL; RAT; INTERLEUKIN-10; INFLAMMATION

Citation

SCIENTIFIC REPORTS, v.7

ISSN
2045-2322
DOI
10.1038/s41598-017-17574-w
URI
http://hdl.handle.net/10203/240045
Appears in Collection
Files in This Item
000417463500037.pdf(2.47 MB)Download
This item is cited by other documents in WoS
⊙ Detail Information in WoSⓡ Click to see webofscience_button
⊙ Cited 25 items in WoS Click to see citing articles in records_button

qr_code

  • mendeley

    citeulike


rss_1.0 rss_2.0 atom_1.0