Aldose Reductase Is Involved in the Development of Murine Diet-Induced Nonalcoholic Steatohepatitis

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	Aldose Reductase Is Involved in the Development of Murine Diet-Induced Nonalcoholic Steatohepatitis
	Qiu, Longxin ; Lin, Jianhui ; Ying, Miao ; Chen, Weiqiang ; Yang, Jinmei ; Deng, Tiantian ; Chen, Jinfeng ; Shi, Duanyu ; Yang, James Y. ; Yang CY(杨朝勇)
刊名	http://dx.doi.org/10.1371/journal.pone.0073591
	2013
关键词	HEPATIC STELLATE CELLS ACTIVATED-RECEPTOR-ALPHA NECROSIS-FACTOR-ALPHA FATTY LIVER-DISEASE GENE-EXPRESSION MICE INHIBITION INDUCTION FIBROSIS INJURY
英文摘要	Natural Science Foundation of Fujian Province, China [2009J01180]; Science Planning Program of Fujian Province, China [2010N0023]; Hepatic aldose reductase (AR) expression is known to be induced in liver diseases, including hepatitis and hepatocellular carcinoma. However, the role of AR in the development of these diseases remains unclear. We performed this current study to determine whether and how AR might be involved in the development of diet-induced nonalcoholic steatohepatitis. Our results showed that the level of AR protein expression was significantly higher in db/db mice fed the methionine-cholinedeficient (MCD) diet than in mice fed the control diet. In parallel with the elevation in AR, steatohepatitis was observed in MCD diet-fed mice, and this diet-induced steatohepatitis was significantly attenuated by lentiviral-mediated knock-down of the AR gene. This suppressive effect of AR knock-down was associated with repressed levels of serum alanine aminotransferase and hepatic lipoperoxides, reduced mRNA and protein expression of hepatic cytochrome P450 2E1 (CYP2E1), and decreased mRNA expression of pro-inflammatory tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6). Moreover, AR-induced elevations on the level of CYP2E1 expression, reactive oxygen species, mRNA expression of TNF-alpha and IL-6 were confirmed in AML12 hepatocytes. Further, lentiviral-mediated knock-down of AR ameliorated MCD diet-induced collagen deposition in the livers of db/db mice. With the improvement in liver fibrosis, the mRNA levels of tissue inhibitor of metalloproteinase-1 (TIMP-1) and matrix metalloproteinase-2 (MMP-2), two genes involved in hepatic fibrogenesis, were found to be significantly suppressed, while TIMP-2 and MMP-13 were unaffected. Together these data indicate that inhibition of AR alleviates the MCD diet-induced liver inflammation and fibrosis in db/db mice, probably through dampening CYP2E1 mediated-oxidative stress and ameliorating the expression of pro-inflammatory cytokines.
语种	英语
出版者	PUBLIC LIBRARY SCIENCE
内容类型	期刊论文
源URL	[http://dspace.xmu.edu.cn/handle/2288/88904]
专题	化学化工－已发表论文
推荐引用方式 GB/T 7714	Qiu, Longxin,Lin, Jianhui,Ying, Miao,et al. Aldose Reductase Is Involved in the Development of Murine Diet-Induced Nonalcoholic Steatohepatitis[J]. http://dx.doi.org/10.1371/journal.pone.0073591,2013.
APA	Qiu, Longxin.,Lin, Jianhui.,Ying, Miao.,Chen, Weiqiang.,Yang, Jinmei.,...&杨朝勇.(2013).Aldose Reductase Is Involved in the Development of Murine Diet-Induced Nonalcoholic Steatohepatitis.http://dx.doi.org/10.1371/journal.pone.0073591.
MLA	Qiu, Longxin,et al."Aldose Reductase Is Involved in the Development of Murine Diet-Induced Nonalcoholic Steatohepatitis".http://dx.doi.org/10.1371/journal.pone.0073591 (2013).