title: Phenanthrene exposure induces cardiac hypertrophy via reducing miR-133a expression by DNA methylation.
abstract: Growing evidence indicates that there is an emerging link between environmental pollution and cardiac hypertrophy, while the mechanism is unclear. The objective of this study was to examine whether phenanthrene (Phe) could cause cardiac hypertrophy, and elucidate the molecular mechanisms involved. We found that: 1) Phe exposure increased the heart weight and cardiomyocyte size of rats; 2) Phe exposure led to enlarged cell size, and increased protein synthesis in H9C2 cells; 3) Phe exposure induced important markers of cardiac hypertrophy, such as atrial natriuretic peptide, B-type natriuretic peptide, and c-Myc in H9C2 cells and rat hearts; 4) Phe exposure perturbed miR-133a, CdC42 and RhoA, which were key regulators of cardiac hypertrophy, in H9C2 cells and rat hearts; 5) Phe exposure induced DNA methyltransferases (DNMTs) in H9C2 cells and rat hearts; 6) Phe exposure led to methylation of CpG sites within the miR-133a locus and reduced miR-133a expression in H9C2 cells; 7) DNMT inhibition and miR-133a overexpression could both alleviate the enlargement of cell size and perturbation of CdC42 and RhoA caused by Phe exposure. These results indicated that Phe could induce cardiomyocyte hypertrophy in the rat and H9C2 cells. The mechanism might involve reducing miR-133a expression by DNA methylation.
authors.affiliation: State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen 361005, China.|Fisheries College, Key Laboratory of Healthy Mariculture for the East China Sea, Ministry of Agriculture, Jimei University, Xiamen, Fujian 361021, P.R. China.
authors.forename: Lixing
authors.initials: L
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen 361005, China.
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Xi
authors.affiliation: State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen 361005, China.|State Key Laboratory of Marine Environmental Science, Xiamen University, Xiamen 361005, China.
authors.forename: Chonggang
authors.initials: C
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen 361005, China.
authors.forename: Youyu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen 361005, China.
authors.forename: Zhibing
authors.initials: Z
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen 361005, China.
authors.forename: Shiqi
authors.initials: S
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen 361005, China.
authors.forename: Yixin
authors.initials: Y
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen 361005, China.|State Key Laboratory of Marine Environmental Science, Xiamen University, Xiamen 361005, China.
authors.forename: Zhenghong
authors.initials: Z
authors.lastname: Zuo
mesh_terms: D000818:Animals; D006332:Cardiomegaly / Q000139:chemically induced* / Q000378:metabolism* / Q000473:pathology; D002460:Cell Line; D018899:CpG Islands; D019175:DNA Methylation / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects*; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis*; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D010616:Phenanthrenes / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C549446:MIRN133 microRNA, rat; D035683:MicroRNAs; D010616:Phenanthrenes; C031181:phenanthrene
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