Alleviation of Toxicity Caused by Overactivation of Pparα through Pparα-Inducible miR-181a2

• Main Authors: Yanjie Cheng (Author), Zhuying Wei (Author), Shengsong Xie (Author), You Peng (Author), Yi Yan (Author), Dan Qin (Author), Shenghui Liu (Author), Yanling Xu (Author), Guangpeng Li (Author), Lisheng Zhang (Author)
• Format: Book
• Published: Elsevier, 2017-12-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

Widely varied compounds, including certain plasticizers, hypolipidemic drugs (e.g., ciprofibrate, fenofibrate, WY-14643, and clofibrate), agrochemicals, and environmental pollutants, are peroxisome proliferators (PPs). Appropriate dose of PPs causes a moderate increase in the number and size of peroxisomes and the expression of genes encoding peroxisomal lipid-metabolizing enzymes. However, high-dose PPs cause varied harmful effects. Chronic administration of PPs to mice and rats results in hepatomegaly and ultimately carcinogenesis. Nuclear receptor protein peroxisome proliferator-activated receptor-α (Pparα) was shown to be required for this process. However, biological adaptations to minimize this risk are poorly understood. In this study, we found that miR-181a2 expression was induced by the Pparα agonist WY-14643. Moreover, exogenous expression of miR-181a-5p dramatically alleviated the cell toxicity caused by overactivation of Pparα. Further studies showed that miR-181a-5p directly targeted the Pparα 3' untranslated region and depressed the Pparα protein level. This study identified a feedback loop between miR-181a-5p and Pparα, which allows biological systems to approach a balance when Pparα is overactivated.

Item Description

2162-2531
10.1016/j.omtn.2017.09.008