Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8258693 | Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease | 2018 | 36 Pages |
Abstract
Atherogenesis is a chronic inflammatory process that involves complex interactions between endothelial dysfunction, lipid deposition and vascular smooth-muscle cell (VSMC) proliferation. However, the molecular mechanism is still unclear. We found that a pro-atherosclerotic factor (oxLDL) induced the expression of Krüppel-like factor 5 (KLF5), which in turn increased miR-29a expression levels. The increased miR-29a was retained within HASMCs and down-regulated Fbw7/CDC4 expression by targeting the 3´UTR of Fbw7/CDC4, subsequently increasing KLF5 stability by reducing the Fbw7/CDC4-dependent ubiquitination of KLF5, forming a positive feedback loop to enhance VSMC proliferation and promote atherogenesis. These results indicate a potentially important role for the oxLDL-activated feedback mechanism in VSMC proliferation and atherogenesis. Suppression of miR-29a may be an effective way to attenuate atherosclerosis. In conclusion, our data are the first to reveal that the regulatory crosstalk between KLF5, miR-29a, and Fbw7/CDC4 cooperatively promotes atherosclerotic development.
Keywords
MIRqRT-PCRKLFHASMCCBPoxLDLVSMCsAtherosclerosiscoronary artery diseaseCell proliferationhuman aortic smooth muscle cellsVascular smooth muscle cellsCADKrüppel-like factorOxidized low-density lipoproteinUntranslated regionsUTR یا untranslated regions MicroRNAquantitative real-time polymerase chain reactionCREB-binding proteinubiquitination
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Authors
Bin Zheng, Cui-ying Zheng, Yu Zhang, Wei-na Yin, Yong-hui Li, Chao Liu, Xin-hua Zhang, Chan-juan Nie, Hong Zhang, Wen Jiang, Shu-feng Liu, Jin-kun Wen,