Curcumin Reorganizes miRNA Expression in a Mouse Model of Liver Fibrosis

Curcumin Reorganizes miRNA Expression in a Mouse Model of Liver Fibrosis
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DOI:
10.7314/apjcp.2012.13.11.5405
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发表时间:
2012-01-01
影响因子:
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通讯作者:
Al-Olayan, Ebtisam M.
Al-Olayan, Ebtisam M.
中科院分区:
其他
文献类型:
--
作者:
Hassan, Zeinab Korany;Al-Olayan, Ebtisam M.

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姜黄素(CM)是一种联苯类化合物,具有抗炎、抗氧化和抗菌等活性。MicroRNAs(MiRNAs)是一种小的非编码RNA,它调节基因的表达和几个生物过程的分子机制。肝纤维化是肝功能障碍和癌症的主要原因,几乎没有有效的治疗方法,强调需要新的方法来控制。本研究通过调节与肝纤维化相关的主要miRNAs(199和200)的表达水平,探讨姜黄素(CM)对肝纤维化的影响。组织病理学检查证实四氯化碳(CCl4)可致大鼠肝纤维化。将小鼠分成3组:第1组:腹腔注射10%CCl4,每周2次,连续4周,然后每周1次,连续4周,然后只注射橄榄油4周。第2组用10%CCl4腹腔注射,每周2次,连续4周,然后每周1次,随后4周每天1次姜黄素(5 mg/只/只/天)。第三组注射橄榄油。实时定量聚合酶链式反应检测miR-199、miR-200及其部分靶基因的表达水平。与对照组相比,肝纤维化组织中miRNA(199和200)水平显著升高。姜黄素的表达水平明显恢复到mir-199和-200的表达水平,相关的靶基因接近正常水平。这是第一个强调姜黄素通过调节miRNAs对肝纤维化的影响的研究。
Curcumin (CM), a biphenyl compound, possesses anti-inflammatory, antioxidant and antimicrobial activity. MicroRNAs (miRNAs) are small noncoding RNAs which regulate gene expression and the molecular mechanisms of several biological processes. Liver fibrosis is a major cause of hepatic dysfunction and cancer and there are few effective therapies emphasizing the need for new approaches to control. The present study was conducted to investigate the effect of curcumin (CM) on liver fibrosis through modulating the expression level of miRNAs (199 and 200), the main miRNAs associated with liver fibrosis. Induction of liver fibrosis by carbon tetrachloride (CCL4) was confirmed by histopathological examination. Mice were divided into 3 groups: group 1 were i.p injected with 10% CCL4 twice weekly for 4 weeks and then once a week for the next 4 weeks followed by 4 weeks with olive oil only. Group 2 were i.p injected with 10% CCL4 twice weekly for 4 weeks and then once a week for the next 4 weeks followed by curcumin (5 mg/mouse/day) once daily for the next 4 weeks. The third group was injected with olive oil. The expression level of miR-199 and miR-200 and some of their targeted genes were measured by real time PCR. miRNA (199 and 200) levels were significantly elevated in liver fibrotic tissues compared to control groups. Curcumin was significantly returned the expression levels of mir-199 and -200 with their associated target gene nearly to their normal levels. This is the first study that highlighted the effect of curcumin on liver fibrosis through regulation of miRNAs.