Genetic analysis of expression profile involved in retinoid metabolism in non-alcoholic fatty liver disease

被引：62

作者：

Ashla, An Afida ^{[1
]}

Hoshikawa, Yoshiko ^{[1
]}

Tsuchiya, Hiroyuki ^{[1
]}

Hashiguchi, Koich ^{[1
]}

Enjoji, Munechika ^{[4
]}

Nakamuta, Makoto ^{[5
]}

Taketomi, Akinobu ^{[6
]}

Maehara, Yoshihiko ^{[6
]}

Shomori, Kohei ^{[2
]}

Kurimasa, Akihiro ^{[1
]}

Hisatome, Ichiro ^{[3
]}

Ito, Hisao ^{[2
]}

Shiota, Goshi ^{[1
]}

机构：

[1] Tottori Univ, Div Mol & Genet Med, Dept Genet Med & Regenerat Therapeut, Grad Sch Med, Yonago, Tottori 6838504, Japan

[2] Tottori Univ, Grad Sch Med, Dept Pathol & Microbiol, Div Organ Pathol, Yonago, Tottori 6838504, Japan

[3] Tottori Univ, Grad Sch Med, Dept Genet Med & Regenerat Therapeut, Div Regenerat Therapeut, Yonago, Tottori 6838504, Japan

[4] Fukuoka Univ, Fac Pharmaceut Sci, Dept Clin Pharmacol, Fukuoka 81401, Japan

[5] Natl Hosp Org, Kyushu Med Ctr, Dept Gastroenterol, Fukuoka, Japan

[6] Kyushu Univ, Grad Sch Med Sci, Dept Surg & Sci, Fukuoka 812, Japan

来源：

HEPATOLOGY RESEARCH | 2010年 / 40卷 / 06期

关键词：

non-alcoholic fatty liver disease; oxidative stress; retinoid metabolism; retinoid target gene; HEPATIC STELLATE CELLS; HEPATOCELLULAR-CARCINOMA; ACID; STEATOHEPATITIS; FIBROSIS; ACTIVATION; PREVENTION; RECEPTORS; CIRRHOSIS; ESTERS;

D O I：

10.1111/j.1872-034X.2010.00646.x

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

Aim: The patients with non-alcoholic fatty liver disease (NAFLD) have been reported to be at greater risk for progression to chronic liver disease including liver cirrhosis (LC). To examine the mechanisms for the progression of NAFLD, a genetic analysis of hepatic expression profile in retinoid metabolism in NAFLD was performed since the loss of retinoid signaling is associated with the progression of liver disease via reactive oxygen species (ROS) generation. Methods: Fifty-one genes, which are associated with retinoid metabolism and action, were examined in thirty six subjects including 17 patients with simple steatosis, 11 with non-alcoholic steatohepatitis (NASH) and eight controls were examined by real-time reverse transcriptase polymerase chain reaction. Immunohistochemical study was also done by 3 kinds of antibodies. Results: Higher expression of CRBP1 LRAT, DGT1/2 and CES1 in NAFLD suggests that mutual conversion between retinyl ester and retinal occurs actively. Expression of ADH1/2/3, RDH5/10/11, DHRS3 and RALDH1/3 was increased in NAFLD, suggesting that oxidation process from retinol to all-trans retinoic acid (ATRA) was enhanced. Importantly, greater expression of CYP26A1 indicated that degradation of ATRA was enhanced in NAFLD. Further, expression of SOD1/2, catalase, thioredoxin and uncoupling protein 2 was also enhanced. Conclusion: Hyperdynamic state of retinoid metabolism is present in the liver tissues with NAFLD, which may be a putative mechanism by which NAFLD progresses to chronic liver disease including LC.

引用

页码：594 / 604

页数：11

共 29 条

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