title: Down-regulation of the miR-543 alleviates insulin resistance through targeting the SIRT1.
abstract: Insulin resistance plays an important role in the development of hypertension, which is seriously detrimental to human health. Recently, Sirtuin-1 (SIRT1) has been found to participate in regulation of insulin resistance. Therefore, further studies focused on the SIRT1 regulators might provide a potential approach for combating insulin resistance and hypertension. Interestingly, in this study, we found that SIRT1 was the target gene of the miR-543 by the Dual-Luciferase Reporter Assay. Moreover, the miR-543 expression notably increased in the insulin-resistant HepG2 cells induced by TNF-α. Further analysis showed that the overexpression of the miR-543 lowered the SIRT1 mRNA and protein levels, resulting in the insulin resistance in the HepG2 cells; the inhibition of miR-543, however, enhanced the mRNA and protein expression of the SIRT1, and alleviated the insulin resistance. Furthermore, the SIRT1 overexpression abrogated the effect of miR-543 on insulin resistance. In addition, the overexpression of the miR-543 by the lentivirus-mediated gene transfer markedly impaired the insulin signaling assessed by the Western blot analysis of the glycogen synthesis and the phosphorylation of Akt and GSK3β. In summary, our study suggested that the downregulation of the miR-543 could alleviate the insulin resistance via the modulation of the SIRT1 expression, which might be a potential new strategy for treating insulin resistance and a promising therapeutic method for hypertension.
authors.affiliation: Departments of Cardiology, Ninth Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, 710054, China.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Hu
authors.affiliation: Departments of Neurology, The 451st Hospital of People's Liberation Army, Xi'an, 710054, China.
authors.forename: Liyi
authors.initials: L
authors.lastname: Chi
authors.affiliation: Departments of Osteology, Xi'an Honghui Hospital, Xi'an Jiaotong University, Xi'an, 710000, China.
authors.forename: Wentao
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Departments of Gereology, Ninth Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, 710054, China.
authors.forename: Tiao
authors.initials: T
authors.lastname: Bai
authors.affiliation: Departments of Cardiology, Ninth Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, 710054, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Departments of Cardiology, Ninth Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, 710054, China.
authors.forename: Zhanbin
authors.initials: Z
authors.lastname: Feng
authors.affiliation: Departments of Peripheral Angiopathy, The First Affiliated Hospital of Xi'an Jiaotong University, No. 277 Yanta West Road, Xi'an, 710061, China. Electronic address: hongyantian9th@tom.com.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Tian
mesh_terms: D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D057809:HEK293 Cells; D056945:Hep G2 Cells; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology*; D035683:MicroRNAs / Q000008:administration & dosage* / Q000235:genetics*; D056564:Sirtuin 1 / Q000378:metabolism*
chemical_list: D007328:Insulin; C577592:MIRN543 microRNA, human; D035683:MicroRNAs; C447939:SIRT1 protein, human; D056564:Sirtuin 1
keywords: Hypertension; Insulin resistance; SIRT1; miR-543