Thioredoxin 1 negatively regulates angiotensin II-Induced cardiac hypertrophy through upregulation of miR-98/let-7

Yanfei Yang, Tetsuro Ago, Peiyong Zhai, Maha Abdellatif, Junichi Sadoshima

研究成果: ジャーナルへの寄稿学術誌査読

127 被引用数 (Scopus)


Rationale: Thioredoxin (Trx)1 inhibits pathological cardiac hypertrophy. MicroRNAs (miRNAs) are small noncoding RNAs that downregulate posttranscriptional expression of target molecules. OBJECTIVES:: We investigated the role of miRNAs in mediating the antihypertrophic effect of Trx1 on angiotensin II (Ang II)-induced cardiac hypertrophy. Methods and Results: Microarray analyses of mature rodent microRNAs and quantitative RT-PCR/Northern blot analyses showed that Trx1 upregulates members of the let-7 family, including miR-98, in the heart and the cardiomyocytes therein. Adenovirus-mediated expression of miR-98 in cardiomyocytes reduced cell size both at baseline and in response to Ang II. Knockdown of miR-98, and of other members of the let-7 family, augmented Ang II-induced cardiac hypertrophy, and attenuated Trx1-mediated inhibition of Ang II-induced cardiac hypertrophy, suggesting that endogenous miR-98/let-7 mediates the antihypertrophic effect of Trx1. Cyclin D2 is one of the predicted targets of miR-98. Ang II significantly upregulated cyclin D2, which in turn plays an essential role in mediating Ang II-induced cardiac hypertrophy, whereas overexpression of Trx1 inhibited Ang II-induced upregulation of cyclin D2. miR-98 decreased both expression of cyclin D2 and the activity of a cyclin D2 3′UTR luciferase reporter, suggesting that both Trx1 and miR-98 negatively regulate cyclin D2. Overexpression of cyclin D2 attenuated the suppression of Ang II-induced cardiac hypertrophy by miR-98, suggesting that the antihypertrophic actions of miR-98 are mediated in part by downregulation of cyclin D2. Conclusions: These results suggest that Trx1 upregulates expression of the let-7 family, including miR-98, which in turn inhibits cardiac hypertrophy, in part through downregulation of cyclin D2.

ジャーナルCirculation research
出版ステータス出版済み - 2月 4 2011

!!!All Science Journal Classification (ASJC) codes

  • 生理学
  • 循環器および心血管医学


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