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Chlorogenic Acid Ameliorates Alcoholic Liver Disease through MiRNA‐mediated Restoration of Mitochondrial Redox System
Author(s) -
Kim Hyunjin,
Pan Jeong Hoon,
Kim Jae Kyeom,
Kim Young Jun,
Lee Jin Hyup,
Park JeenWoo
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.46.3
Subject(s) - alcoholic liver disease , microrna , mitochondrion , epigenetics , biology , microbiology and biotechnology , liver injury , steatosis , cancer research , biochemistry , pharmacology , cirrhosis , gene , medicine , endocrinology
MicroRNAs (miRNA) play essential roles in virtually all cellular and biological processes in liver development, differentiation and homeostasis. Altered expression levels of miRNA were observed in patients with alcoholic liver diseases (ALD) including liver steatosis, cirrhosis and hepatocellular carcinoma. Mitochondria, the main organelles involved in intracellular ROS production, play central roles in modulating redox‐dependent cellular processes, such as metabolism and apoptosis, and disruptions of the mitochondrial redox metabolism are closely associated with ALD. Dietary polyphenols are a versatile group of phytochemicals with many potentially beneficial activities in terms of disease prevention. It is recently reported that the dietary components can selectively activate or inactivate gene expression through epigenetic regulation including alteration in the miRNA expression to exhibit the physiological roles in the prevention of various diseases. In the present study therefore, we investigated if chlorogenic acid (CGA), a potent bioactive polyphenol present in vegetables, can selectively modulate gene expression through miRNA regulation to elicit their beneficial effects. Here we show that CGA protect alcohol‐induced liver injury in mice and these functions of CGA are closely associated with suppression of hepatic apoptosis and inflammation mediated by mitochondrial ROS. Of note, in the global miRNA profiling analysis, hepatic miRNAs were either elevated or suppressed in response to CGA supplementation. Predictions by Ingenuity Pathway Analysis indicated that some of miRNAs target genes are related with hepatic mitochondrial redox metabolism. Moreover, the epigenetic mechanisms are responsible for, at least in part, effects of CGA against the alcoholic liver injury through restoration of the mitochondrial redox system. Taken together, our results highlight the importance of miRNA in the regulation of mitochondrial redox systems and demonstrate that CGA plays a key role in modulating the alcohol‐induced liver injury through miRNA modulation. Further investigations are warranted regarding the net downstream effects of miRNA modulation as pertains to ALD. Support or Funding Information This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (Grant No. NRF‐2015R1A4A1042271).