Silibinin Ameliorates O-GlcNAcylation and Inflammation in a Mouse Model of Nonalcoholic Steatohepatitis

The mechanisms underlying the progression to non-alcoholic steatohepatitis (NASH) remain to be elucidated. In the present study, we aimed to identify the proteins involved in the pathogenesis of liver tissue inflammation and to investigate the effects of silibinin, a natural polyphenolic flavonoid,...

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Main Authors:	Su Jin Lee, Min Jung Nam, Da Eun Lee, Jeen-Woo Park, Beom Sik Kang, Dong-Seok Lee, Hyun-Shik Lee, Oh-Shin Kwon
Format:	Article
Language:	English
Published:	MDPI AG 2018-07-01
Series:	International Journal of Molecular Sciences
Subjects:	silibinin O-GlcNAcylation non-alcoholic steatohepatitis proteomics inflammation
Online Access:	http://www.mdpi.com/1422-0067/19/8/2165

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spelling	doaj-art-968ace33b6454fc38a3b709c44f1d3c22018-08-22T07:58:42ZengMDPI AGInternational Journal of Molecular Sciences1422-00672018-07-01198216510.3390/ijms19082165ijms19082165Silibinin Ameliorates O-GlcNAcylation and Inflammation in a Mouse Model of Nonalcoholic SteatohepatitisSu Jin Lee0Min Jung Nam1Da Eun Lee2Jeen-Woo Park3Beom Sik Kang4Dong-Seok Lee5Hyun-Shik Lee6Oh-Shin Kwon7School of Life Science, College of Natural Science, Kyungpook National University, Daegu 41566, KoreaSchool of Life Science, College of Natural Science, Kyungpook National University, Daegu 41566, KoreaSchool of Life Science, College of Natural Science, Kyungpook National University, Daegu 41566, KoreaSchool of Life Science, College of Natural Science, Kyungpook National University, Daegu 41566, KoreaSchool of Life Science, College of Natural Science, Kyungpook National University, Daegu 41566, KoreaSchool of Life Science, College of Natural Science, Kyungpook National University, Daegu 41566, KoreaSchool of Life Science, College of Natural Science, Kyungpook National University, Daegu 41566, KoreaSchool of Life Science, College of Natural Science, Kyungpook National University, Daegu 41566, KoreaThe mechanisms underlying the progression to non-alcoholic steatohepatitis (NASH) remain to be elucidated. In the present study, we aimed to identify the proteins involved in the pathogenesis of liver tissue inflammation and to investigate the effects of silibinin, a natural polyphenolic flavonoid, on steatohepatitis. We performed comparative proteomic analysis using methionine and choline-deficient (MCD) diet-induced NASH model mice. Eighteen proteins were identified from the two-dimensional proteomic analysis, which are not only differentially expressed, but also significantly improved, by silibinin treatment. Interestingly, seven of these proteins, including keratin cytoskeletal 8 and 18, peroxiredoxin-4, and protein disulfide isomerase, are known to undergo GlcNAcylation modification, most of which are related to structural and stress-related proteins in NASH model animals. Thus, we primarily focused on how the GlcNAc modification of these proteins is involved in the progression to NASH. Remarkably, silibinin treatment alleviates the severity of hepatic inflammation along with O-GlcNAcylation in steatohepatitis. In particular, the reduction of inflammation by silibinin is due to the inhibition of the O-GlcNAcylation-dependent NF-κB-signaling pathway. Therefore, silibinin is a promising therapeutic agent for hyper-O-GlcNAcylation as well as NASH.http://www.mdpi.com/1422-0067/19/8/2165silibininO-GlcNAcylationnon-alcoholic steatohepatitisproteomicsinflammation
institution	Open Data Bank
collection	Open Access Journals
building	Directory of Open Access Journals
language	English
format	Article
author	Su Jin Lee Min Jung Nam Da Eun Lee Jeen-Woo Park Beom Sik Kang Dong-Seok Lee Hyun-Shik Lee Oh-Shin Kwon
spellingShingle	Su Jin Lee Min Jung Nam Da Eun Lee Jeen-Woo Park Beom Sik Kang Dong-Seok Lee Hyun-Shik Lee Oh-Shin Kwon Silibinin Ameliorates O-GlcNAcylation and Inflammation in a Mouse Model of Nonalcoholic Steatohepatitis International Journal of Molecular Sciences silibinin O-GlcNAcylation non-alcoholic steatohepatitis proteomics inflammation
author_facet	Su Jin Lee Min Jung Nam Da Eun Lee Jeen-Woo Park Beom Sik Kang Dong-Seok Lee Hyun-Shik Lee Oh-Shin Kwon
author_sort	Su Jin Lee
title	Silibinin Ameliorates O-GlcNAcylation and Inflammation in a Mouse Model of Nonalcoholic Steatohepatitis
title_short	Silibinin Ameliorates O-GlcNAcylation and Inflammation in a Mouse Model of Nonalcoholic Steatohepatitis
title_full	Silibinin Ameliorates O-GlcNAcylation and Inflammation in a Mouse Model of Nonalcoholic Steatohepatitis
title_fullStr	Silibinin Ameliorates O-GlcNAcylation and Inflammation in a Mouse Model of Nonalcoholic Steatohepatitis
title_full_unstemmed	Silibinin Ameliorates O-GlcNAcylation and Inflammation in a Mouse Model of Nonalcoholic Steatohepatitis
title_sort	silibinin ameliorates o-glcnacylation and inflammation in a mouse model of nonalcoholic steatohepatitis
publisher	MDPI AG
series	International Journal of Molecular Sciences
issn	1422-0067
publishDate	2018-07-01
description	The mechanisms underlying the progression to non-alcoholic steatohepatitis (NASH) remain to be elucidated. In the present study, we aimed to identify the proteins involved in the pathogenesis of liver tissue inflammation and to investigate the effects of silibinin, a natural polyphenolic flavonoid, on steatohepatitis. We performed comparative proteomic analysis using methionine and choline-deficient (MCD) diet-induced NASH model mice. Eighteen proteins were identified from the two-dimensional proteomic analysis, which are not only differentially expressed, but also significantly improved, by silibinin treatment. Interestingly, seven of these proteins, including keratin cytoskeletal 8 and 18, peroxiredoxin-4, and protein disulfide isomerase, are known to undergo GlcNAcylation modification, most of which are related to structural and stress-related proteins in NASH model animals. Thus, we primarily focused on how the GlcNAc modification of these proteins is involved in the progression to NASH. Remarkably, silibinin treatment alleviates the severity of hepatic inflammation along with O-GlcNAcylation in steatohepatitis. In particular, the reduction of inflammation by silibinin is due to the inhibition of the O-GlcNAcylation-dependent NF-κB-signaling pathway. Therefore, silibinin is a promising therapeutic agent for hyper-O-GlcNAcylation as well as NASH.
topic	silibinin O-GlcNAcylation non-alcoholic steatohepatitis proteomics inflammation
url	http://www.mdpi.com/1422-0067/19/8/2165
_version_	1612679906465939456

Silibinin Ameliorates O-GlcNAcylation and Inflammation in a Mouse Model of Nonalcoholic Steatohepatitis

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